key: cord-022292-msz4au4b
authors: Gershan, William M.
title: Cough
date: 2009-05-15
journal: Practical Strategies in Pediatric Diagnosis and Therapy
DOI: 10.1016/b978-0-7216-9131-2.50006-3
sha: 
doc_id: 22292
cord_uid: msz4au4b

nan

The previous response or lack of response to some therapies for recurrent and chronic cough can provide important information (see Table 2 -3). Furthermore, some coughs may be caused or worsened by medications (Table 2-4) .

A history of accompanying signs or symptoms, whether localized to the respiratory tract (wheeze, stridor) or elsewhere (failure to thrive, frequent malodorous stools) can give important clues (Table 2-5; see  Tables 2-2 and 2-3) . It is essential to remember that the daily language of the physician is full of jargon that may be adopted by parents but with a different meaning from that understood by physicians. If a parent says that a child "wheezes" or "croups" or is "short of breath," it is important to find out what the parent means by that term.

Because many disorders of childhood have genetic or nongenetic familial components, the family history can provide helpful information:

Are there older siblings with cystic fibrosis (CF) or asthma? Is there a coughing sibling whose kindergarten class has been closed because of pertussis?

Similarly, the key to today's problems may be found in the past:

Was the child premature and, if so, did he or she spend a month on the ventilator, and does he or she now have chronic lung disease (bronchopulmonary dysplasia)? Did the toddler choke on a carrot or other food 3 months ago? Did the child receive a bone marrow transplant a year ago? Is the child immunized? Did the infant have a tracheoesophageal fistula repaired in the neonatal period? *Infections include upper (pharyngitis, sinusitis, tracheitis, rhinitis, otitis) and lower (pneumonia, abscess, empyema) respiratory tract disease. † Anatomic abnormality includes tracheobronchomalacia, tracheoesophageal fistula, vascular ring, abnormal position, or take-off of large bronchi. 1 common; 2 less common; 3 much less common. CF, cystic fibrosis; GER, gastroesophageal reflux.

Initial inspection often reveals the seriousness of an illness:

Is the child struggling to breathe (dyspnea)? Does the child have an anxious look? Can the child be calmed or engaged in play? Is the child's skin blue (representing cyanosis) or ashen? Does the child appear wasted, with poor growth that may indicate a chronic illness?

The respiratory rate is often elevated with parenchymal lung disease or extrathoracic obstruction. Respiratory rates vary with the age of the child (Fig. 2-3) and with pulmonary infection, airway obstruction, activity, wakefulness and sleep, fever, metabolic acidosis, and anxiety.

Odors may also give helpful clues. Does the examining room or the clothing smell of stale cigarette smoke? Is there a foul odor from a diaper with a fatty stool, which may suggest pancreatic insufficiency and CF? Is the child's breath malodorous, as can be noticed in sinusitis, nasal foreign body, lung abscess, or bronchiectasis?

It has been said that the examination of the lungs begins at the fingertips. Cyanotic nail beds suggest hypoxemia, poor peripheral circulation, or both. The examiner looks for the presence of digital clubbing ( Fig. 2-4) , which makes asthma or acute pneumonia extremely unlikely. The absence of digital clubbing but a history of severe chronic cough in an older child makes CF unlikely.

The shape of the chest gives information. Is the anteroposterior (AP) diameter increased, which indicates hyperinflation of the lungs from obstruction of small airways (asthma, bronchiolitis, CF)? Is this diameter small, as can be seen with some restrictive lung diseases with small lung volumes (muscular dystrophy, spinal muscular atrophy)? The normal infant has a "round" chest configuration, with the AP diameter of the chest about 84% of the transverse (lateral) diameter. With growth, the chest becomes more flattened in the AP dimension, and the AP-to-transverse ratio is closer to 70% to 75%. Although obstetric calipers can be used to give an objective assessment of the AP diameter of the chest, most clinicians rely on their subjective assessment of whether the diameter is increased: Does the patient look "barrel-chested"?

Intercostal, subcostal, suprasternal, and supraclavicular retractions (inspiratory sinking in of the soft tissues) indicate increased effort of breathing and reflect both the contraction of the accessory muscles of respiration and the resulting difference between intrapleural and extrathoracic pressure. Retractions occur most commonly with obstructed airways (upper or lower), but they may occur with any condition leading to the use of the accessory muscles. Any retractions other than the mild normal depressions seen between an infant's lower ribs indicate a greater-than-normal work of breathing.

Less easy to notice than intercostal retractions is their bulging out with expiration in a child with expiratory obstruction (asthma). Contraction of the abdominal muscles with expiration is easier to notice and is another indication that a child is working harder than normal to push air out through obstructed airways.

Inspection of the spine may reveal kyphosis or scoliosis. There is a risk of restrictive lung disease or static pneumonia if the curvature is severe.

Palpating the trachea, particularly in infants, may reveal a shift to one side, which suggests loss of volume of the lung on that side or extrapulmonary gas (pneumothorax) on the other side. Placing one hand on each side of the chest while the patient breathes may enable the examiner to detect asymmetry of chest wall movement, either in timing or in degree of expansion. The former indicates a partial bronchial obstruction, and the latter suggests a smaller lung volume, voluntary guarding, or diminished muscle function on one side. Palpating the abdomen gently during expiration may allow the examiner to feel the contraction of the abdominal muscles in cases of expiratory obstruction. Palpation for tactile fremitus, the transmitted vibrations of the spoken word ("ninety-nine" is the word often used to accentuate these vibrations), helps determine areas of increased parenchymal density and hence increased fremitus (as in pneumonic consolidation) or decreased fremitus (as in pneumothorax or pleural effusion).

The percussion note determined by the examiner's tapping of one middle finger on the middle finger of the other hand, which is firmly placed over the patient's thorax, may be dull over an area of consolidation or effusion and hyperresonant with air trapping. Percussion can also be used to determine diaphragmatic excursion. The lowest level of resonance at inspiration and expiration determines diaphragmatic motion.

Because lung sounds tend to be higher-pitched than heart sounds, the diaphragm of the stethoscope is better suited to pulmonary auscultation than is the bell, whose target is primarily the lower-pitched heart sounds (Table 2-6). The adult-sized stethoscope generally is far superior to the smaller pediatric or neonatal diaphragms, even for listening to small chests, because its acoustics are better. The two-headed stethoscope enables the user to hear homologous segments of both lungs simultaneously in order to identify instances in which there is a delay in air entry or exit. The traditional single-headed stethoscope is adequate in most children with cough. The ability to recognize normal breath sounds comes with practice ( Fig. 2-6 ).

Adventitious sounds come in a few varieties, namely, stridor, crackles, rhonchi, and wheezes. Other sounds should be described in clear, everyday language.

Stridor is a continuous musical sound usually heard on inspiration and is caused by narrowing in the extrathoracic airway, as with croup or laryngomalacia.

Crackles are discontinuous, representing the popping open of air-fluid menisci as the airways dilate with inspiration. Fluid in 

Very common and suggests the diagnosis; ++, common; +, uncommon; -, almost never and makes examiner question the diagnosis. Respiratory Disorders larger airways causes crackles early in inspiration (congestive heart failure); crackles that tend to be a bit lower in pitch ("coarse" crackles) than the early, higher-pitched ("fine") crackles are associated with fluid in small airways (pneumonia). Although crackles usually signal the presence of excess airway fluid (pneumonia, pulmonary edema), they may also be produced by the popping open of noninfected fibrotic or atelectatic airways. Fine crackles are not audible at the mouth, whereas coarse crackles may be. Crackles is the preferred term, rather than the previously popular "rales." Rhonchi, or "large airway sounds," are continuous gurgling or bubbling sounds typically heard during both inhalation and exhalation. These sounds are caused by movement of fluid and secretions in larger airways (asthma, viral URI). Rhonchi, unlike other sounds, may clear with coughing.

Wheezes are continuous musical sounds (lasting longer than 200 milliseconds), caused by vibration of narrowed airway walls, as with asthma, and perhaps vibration of material within airway lumens. These sounds are much more commonly heard during expiration than inspiration.

The chest radiograph is often the most useful diagnostic test in the evaluation of the child with cough. Table 2 -7 highlights some of the radiographic features of the most common causes of cough in pediatric patients. Radiographic findings are often similar for a number of disorders, and thus these studies may not indicate a definitive diagnosis. Chest films are normal in children with psychogenic (habit) cough and in children with sinusitis or gastroesophageal reflux (GER) as the primary cause of cough. A normal chest radiograph indicates the unlikelihood of pneumonia caused by respiratory syncytial virus (RSV), influenza, parainfluenza, adenovirus, Chlamydia species, or bacteria. Although children with cough resulting from CF, Mycoplasma species, tuberculosis, aspiration, a bronchial foreign body, or an anatomic abnormality usually have abnormal chest radiographs, a normal radiograph does not exclude these diagnoses. Hyperinflation of the lungs is commonly seen on chest films of infants with RSV bronchiolitis or Chlamydia pneumonia, and a lobar or round (coin lesion) infiltrate is the radiographic hallmark of bacterial pneumonia. The diagnosis of sinusitis cannot be sustained with normal sinuses on radiograph or computed tomography (CT) scan.

The white blood cell (WBC) count may help exclude or include certain entities for a differential diagnosis, but, with the possible exception of pertussis, can seldom establish a diagnosis with certainty. A WBC count of 35,000 with 85% lymphocytes strongly suggests pertussis, but not every child with pertussis presents such a clear hematologic picture. The presence of a high number or large proportions of immature forms of WBCs suggests an acute process, such as a bacterial infection. Immunoglobulins provide supportive evidence for a few diagnoses, such as chlamydial infection, which rarely occurs without elevated serum concentrations of immunoglobulins G and M.

Specific bacteriologic or virologic diagnoses can be made in a number of disorders causing cough, including RSV, influenza, parainfluenza, adenovirus, and Chlamydia pneumonia. In most cases, these diagnoses are based on culturing the organism from nasopharyngeal washings. In some cases, the viruses can be rapidly identified with immunofluorescence or amplification of viral genome through polymerase chain reaction (PCR). In bacterial pneumonia, the offending organism can be cultured from the blood in a small proportion (10%) of patients. A positive culture provides definitive diagnosis, but a negative culture specimen is not helpful. Throat cultures are seldom helpful (except in CF) in identifying lower respiratory tract organisms. Sputum cultures and Gram stains may help guide initial empirical therapy in older patients with pneumonia or purulent bronchitis, but their ability to identify specific causative organisms with certainty (again with the exception of CF) has not been shown clearly.

Infants and young children usually do not expectorate but, rather, swallow their sputum. Specimens obtained via bronchoscopy may be contaminated by mouth flora, but heavy growth of a single organism in the presence of polymorphonuclear neutrophils certainly supports the organism's role in disease. If pleural fluid or fluid obtained directly from the lung via needle aspiration is cultured, the same rules apply: Positive cultures are definitive, but negative cultures are not. Bacterial antigen detection in serum or urine by various techniques (latex agglutination) can help identify pneumococcus and Haemophilus influenzae type b.

A number of specific tests can help to establish diagnoses in a child with cough (see Table 2 -7). These include a positive response to bronchodilators in a child with asthma; visualizing the red, swollen epiglottis in epiglottitis (to be done only under very controlled conditions, as described later); the bronchoscopic visualization of the peanut, plastic toy, or other offender in foreign body aspiration; a positive purified protein derivative in tuberculosis; and several studies of the esophagus in GER. Several imaging techniques, such as CT or magnetic resonance imaging (MRI), can help to delineate various intrathoracic anatomic abnormalities. Finally, multiple tests can be employed to confirm the diagnosis of CF (Table 2-8).

Infections are the most common cause of acute cough in all age groups and are responsible for some chronic coughs. The age of the patient has a large impact on the type of infection.

Viral upper respiratory infections (common cold); croup (laryngotracheobronchitis); viral bronchiolitis, particularly with RSV; and viral pneumonia are the most frequently encountered respiratory tract infections and hence the most common causes of cough in infancy. Viral illness may predispose to bacterial superinfection (croup and Staphylococcus aureus tracheitis or influenza and H. influenzae pneumonia).

Cold symptoms and signs usually include stuffy nose, with nasal discharge (rhinorrhea); sore throat and sneezing frequently occur. There may be fever, constitutional signs (irritability, myalgias, headache), or both. Cough is common and may persist for 5 to 7 days. The mechanism by which upper respiratory infections cause cough in children is undetermined. In adults, it is generally thought that "postnasal drip"-that is, nasal or sinus secretions draining into the posterior nasopharynx-causes cough and, in fact, may be one of the most frequent causes of cough. Indeed, sinus CT in older patients , or the phalangeal depth ratio, is normally less than 1 but increases to more than 1 with finger clubbing. The DPD/IPD ratio can be measured with calipers or, more accurately, with finger casts. The hyponychial angle is measured from lateral projections of the finger contour on a magnifying screen and is normally less than 180 degrees but greater than 195 degrees with finger clubbing. Schamroth's sign is useful for bedside assessment. The dorsal surfaces of the terminal phalanges of similar fingers are placed together. With clubbing, the normal diamond-shaped aperture or "window" at the bases of the nail beds disappears, and a prominent distal angle forms between the end of the nails. In normal subjects, this angle is minimal or nonexistent. ( Whispering pectoriloquy produces clearer sounding whispered words (e.g., "ninety-nine").

PMI, point of maximal impulse.

with colds often reveals involvement of the sinus mucosa. Whether this is true in children remains undetermined. Other authorities believe that cough in a child with a cold indicates involvement (inflammation or bronchospasm) of the lower respiratory tract. The physician's bias on this matter will probably influence how to treat the child with cough accompanying a cold. In adults, the cough of the common cold may respond to a combination antihistaminedecongestant preparation, presumably from the decreased postnasal drip. It is uncertain whether such treatment is effective or indicated in children, particularly young infants, in whom toxicity of the drugs may be a greater concern than in adults. Common viral pathogens include rhinovirus, RSV, and parainfluenza virus. The differential diagnosis includes allergic rhinitis, which often demonstrates clear nasal secretions with eosinophils and pale nasal mucosa, in contrast to mucopurulent nasal secretions with neutrophils and erythematous mucosa.

Infectious croup (see Chapter 5) is most common in the first 2 years of life. Its most dramatic components are the barking ("croupy") cough and inspiratory stridor, which appear a few days after the onset of a cold. In most cases, the patient has a low-grade fever, and the disease resolves within a day or two. In severe cases, the child can be extremely ill and is at risk for complete laryngeal obstruction. There may be marked intercostal and suprasternal retractions and cyanosis. Stridor at rest signifies significant obstruction. Diminishing stridor in a child who is becoming more comfortable is a good sign, but diminishing stridor in and of itself is not necessarily good: If the child becomes fatigued because of the tremendous work of breathing through an obstructed airway and can no longer breathe effectively, smaller-than-needed tidal volumes make less noise. Low yield on culture in paroxysmal stage.

Pleural effusion relatively common. 6 Blood culture positive in 10%; needle aspiration of pleural fluid or lung fluid may yield organism; bacterial antigen in urine. In older infants and children, common pathogens include pneumococci and group A streptococci; Staphylococcus aureus is rare and may be associated with pneumatoceles or empyema. 7 Localized hyperinflation is common; localized atelectasis in common; inspiratory-expiratory films may show ball-valve obstruction. 8 Esophageal biopsy specimen shows esophagitis. 9 Multilobular or multisegmental, dependent lobes. 10 (?) Lipid-laden macrophages from bronchoscopy or gastric washings; barium swallow or radionuclide study showing aspiration.

Right-sided arch, mass effect on airways, mass identified; magnetic resonance imaging (MRI).

Bronchoscopy; computed tomography; MRI.

+++, almost always-if not present, must question diagnosis; ++, common; +, less common; -, seldom-if present, must question diagnosis.

+Bld Cult, blood culture may be positive; Bronch, bronchoscopy can reveal the foreign body; Diff, diffuse or scattered; ↑ EOS, increased eosinophil count; Esoph pH, prolonged esophageal pH probe monitoring; GE, gastroesophageal; Hyper, hyperinflated; Ig, immunoglobulin; Infil, infiltrates;

↑ LY, increased lymphocyte count; +NP Cult, nasopharyngeal culture positive for specific organism; Paraflu, parainfluenza virus; PCR, polymerase chain reaction;

↑ PMN, increased polymorphonuclear neutrophil count; PPD, purified protein derivative (TB); RAD, reactive airways disease; RSV, respiratory syncytial virus; TB, tuberculosis;

↑ WBC, increased white blood cell count.

It is important to distinguish croup from epiglottitis in the child with harsh, barking cough and inspiratory stridor because the natural histories of the two diseases are quite different (see Table 2 -7). Epiglottitis occurs more commonly in toddlers than in infants (see Chapter 5).

Treatment of mild croup is usually not needed. For decades, pediatricians have recommended putting a child with croup in a steamy bathroom or driving to the office or emergency room with the car windows rolled down. (It is likely that these remedies are effective because of the heat exchange properties of the upper airway; air that is cooler or more humid than the airway mucosa will serve to cool the mucosa, thus causing local vasoconstriction and probably decreasing local edema.)

In a child who has stridor at rest, hospitalization is indicated. Symptomatic, often dramatic relief through decreased laryngeal edema can usually be achieved with aerosolized racemic epinephrine (2.25% solution, 0.25 to 0.5 mL/dose). It is essential to remember that the effects of the epinephrine are transient, lasting only a few hours, although the course of the illness is often longer. The result is that when the racemic epinephrine's effect has worn off, the child's cough and stridor will probably be as bad or even worse than before the aerosol was administered. This is not a "rebound" effect: The symptoms are not worse because of the treatment but, rather, because of the natural progression of the viral illness. Repeating the aerosol will probably again have a beneficial effect and reduce the likelihood of requiring a tracheotomy or endotracheal intubation. A child who responds favorably to such an aerosol needs to be observed for several hours because further treatment may be needed. A single dose of dexamethasone (0.6 mg/kg orally, intramuscularly, or intravenously) reduces the severity and hastens recovery. Aerosolized steroids (budesonide) may also be effective in patients with mild to moderately severe croup.

Bronchiolitis is a common and potentially serious lower respiratory tract disorder in infants (see Chapters 3 and 5). It is caused usually by RSV but on occasion by parainfluenza, influenza, or adenovirus. It occurs in the winter months, often in epidemics. RSV bronchiolitis is seen uncommonly in children older than 4 years. Typically, "coldlike" symptoms of rhinorrhea precede the harsh cough, increased respiratory rate, and retractions. Respiratory distress and cyanosis can be severe. The child's temperature is seldom elevated above 38°C.

The chest is hyperinflated, widespread crackles are audible on inspiration, and wheezing marks expiration. The most striking laboratory abnormalities are in the chest radiograph, which invariably reveals hyperinflation, as depicted by a depressed diaphragm, with an enlarged retrosternal air space in as many as 60% of patients, peribronchial thickening in approximately 50%, and consolidation and/or atelectasis in 10% to 25%.

The diagnosis is confirmed with demonstration of RSV by immunofluorescent stain or PCR of nasopharyngeal washings. In most cases, no treatment is needed because the disease does not interfere with the infant's eating or breathing. Apnea is a common complication of RSV bronchiolitis in young infants and may necessitate close monitoring. In severe cases, often those in which there is underlying chronic heart, lung, or immunodeficiency disease, RSV can be life-threatening. In these cases, hospital care with supplemental oxygen and intravenous fluids is indicated. The effect of aerosolized bronchodilators is not clear but is probably beneficial in some infants. The aerosolized antiviral agent ribavirin may be beneficial for the sickest infants. It is expensive and difficult to administer; it needs to be given 12 to 18 hours per day (some studies advocate 2 hours three times a day) and may block ventilator tubing and valves. Ribavirin may improve oxygenation but should not be used in lieu of mechanical ventilation in patients with hypoxia and hypercarbia (respiratory failure).

Viral pneumonia can be similar to RSV bronchiolitis in its manifestation, with cough and tachypnea, after a few days of apparent upper respiratory infection. There can be variable degrees of fever and of overall illness. Infants and children with viral pneumonia may appear relatively well or, particularly with adenovirus, may have a rapidly progressive course, which ends in death within a few days after the onset of illness. Frequent symptoms include poor feeding, cough, cyanosis, fever (some patients may be afebrile), apnea, and IRT, immunoreactive trypsinogen. Respiratory Disorders rhinorrhea. Frequent signs include tachypnea, retractions, crackles, and cough. Cyanosis is less common. The most common agents causing viral pneumonia in infancy and childhood are RSV, influenza, and parainfluenza. Adenovirus is less common, but it is important because it can be severe and leave residua, including bronchiectasis and bronchiolitis obliterans. Adenovirus pneumonia is often accompanied by conjunctivitis and pharyngitis, in addition to leukocytosis and an elevated erythrocyte sedimentation rate (ESR); the ESR and leukocyte count are usually not elevated in other types of viral pneumonia. Additional viral agents include enteroviruses and rhinovirus. Radiographs most often reveal diffuse, bilateral peribronchial infiltrates, with a predilection for the perihilar regions, but occasionally lobar infiltrates are present. Pleural effusions are not common. On occasion, if an infant is extremely ill, bronchoscopy with bronchoalveolar lavage may be indicated to isolate the virus responsible for the pneumonia.

Treatment is largely supportive, with oxygen and intravenous fluids. Mechanical ventilation may be necessary in a small minority of infants. In young infants, the afebrile pneumonia syndrome may be caused by Chlamydia, Ureaplasma, or Mycoplasma species; cytomegalovirus; or Pneumocystis carinii. In this syndrome, cough and tachypnea are common. Severe pneumonia may develop in neonates as a result of herpes simplex.

Pertussis is an extremely important cause of lower respiratory tract infection in infants and children. The causative organism, Bordetella pertussis, has a tropism for tracheal and bronchial ciliated epithelial cells; thus, the disease is primarily bronchitis, but spread of the organism to alveoli, or secondary invasion by other bacteria, can cause pneumonia. The disease can occur at any age, from early infancy onward, although its manifestations in young infants and in those who have been partially immunized may be atypical.

Most commonly, pertussis has three stages:

• catarrhal, in which symptoms are indistinguishable from the common cold • paroxysmal, dominated by repeated forceful, paroxysmal coughing spells; many spells may be punctuated by an inspiratory "whoop," post-tussive emesis, or both • convalescent, in which the intensity and frequency of coughing spells gradually diminish Each stage typically lasts 1 to 2 weeks, except the paroxysmal stage, which lasts many weeks. The Chinese term for pertussis translates to "100 days of cough." Most children are entirely well between coughing spells, when physical findings are remarkably benign. Infants younger than 3 months of age may have the most severe illness, and in this age group, the rate of mortality from pertussis is as high as 40%.

Diagnosis can be difficult because the definitive result-namely, culturing the organism from nasopharyngeal secretions-requires special culture medium (Bordet-Gengou, which must be prepared fresh for each collection). Culture specimens are much less likely to be positive during the paroxysmal stage than during the catarrhal stage, when the diagnosis is not being considered. Fluorescent antibody stains (for the antigen) of secretions are also helpful if they are positive, but, similarly, they are more likely to be positive before the paroxysmal stage. Serum antibodies against B. pertussis may occasionally be helpful, although they are often difficult to interpret in immunized individuals. Perhaps the laboratory test that is most helpful is the WBC count, which is typically elevated; values are as high as 20,000 to 50,000, with lymphocytes predominating. PCR is also useful. Chest radiographic findings are nonspecific. Infants with severe disease may require hospitalization.

Treatment is largely supportive, with oxygen, fluids, and small frequent feedings for patients who do not tolerate their normal feedings. Treatment with erythromycin estolate (50 mg/kg/day for 14 days, every 6 hours, orally) decreases infectivity and may ameliorate the course of the disease if given during the catarrhal stage. Studies suggest that azithromycin or clarithromycin may also be effective. In some patients, aerosolized bronchodilators (albuterol) or systemic steroids may help, although such treatment is controversial. Cough suppressants are not helpful, but good hydration, oxygenation, and nutrition, in addition to not disturbing the infant, are important.

Complications include those related to severe coughing (Table 2-9) and those specific to pertussis, such as seizures and encephalopathy. Pertussis is prevented by three primary immunizations (at 2, 4, and 6 months of age) and regular booster immunizations at 15 to 18 months and 4 to 6 years of age. Pertussis infection produces lifelong immunity.

Chlamydia trachomatis can cause pneumonia in young infants, particularly those aged 3 to 12 weeks. Cough, nasal congestion, lowgrade or no fever, and tachypnea are common. Conjunctivitis is an important clue to chlamydial disease but is present in only 50% of infants with chlamydial pneumonia at the time of presentation. Affected infants may have a paroxysmal cough similar to that of pertussis, but post-tussive emesis is less common. Crackles are commonly heard on auscultation, but wheezing is much less common than the overinflated appearance of the lungs on radiographs would suggest. The organism may be recovered from the nasopharynx by culture or antigen testing. The complete blood cell count may reveal eosinophilia. Chlamydial infection responds to oral erythromycin therapy (40 to 50 mg/kg/day, every 6 hours for 10 to 14 days). 

Ureaplasma urealyticum pneumonia is difficult to diagnose but causes cough in some infants. There are no particularly outstanding features to distinguish this relatively uncommon infection from viral pneumonias.

Bacterial pneumonia is relatively less common in infants than is viral pneumonia but can cause severe illness, with cough, respiratory distress, and fever. Chest films are strikingly abnormal; the WBC count is elevated. Treatment is with broad-spectrum intravenous antibiotics effective against pneumococci, group A (possibly B) streptococci, and, if illness is severe, S. aureus. Cefotaxime with or without nafcillin may be effective.

In early childhood, as children attend day care and nursery schools, they are constantly exposed to respiratory viruses to which they have little or no immunity (e.g., rhinoviruses, adenoviruses, parainfluenza, and coxsackievirus). Such children may have as many as 6 to 8 or even more colds in a year. The remarks concerning colds and cough in infants (see previous discussion) apply to this older age group. The differential diagnosis of rhinorrhea is noted in Table 2 -10.

The sinuses may become the site for viral and subsequent secondary bacterial infection spreading from the nasopharynx (Fig. 2-7) . The signs and symptoms are usually localized, including nasal congestion, a feeling of "fullness" or pain in the face ( Fig. 2-8) , headache, sinus tenderness, day or night cough, and fever. Maxillary toothache, purulent nasal discharge for more than 10 days, a positive transillumination (opacification), and a poor response to oral antihistamines or nasal decongestants are important clues. Sinus radiographs or (more accurate) CT scan may facilitate the diagnosis of sinusitis by demonstrating opacification of the sinus with mucosal thickening. Sinusitis is thought to be a cause of cough in adults and can probably be listed, with lower certainty, as a cause of cough in children.

Sinusitis is frequently seen in other conditions known to cause cough, especially CF, asthma, and ciliary dyskinesia. It may be difficult to ascertain whether the cough is a direct result of the sinus infection or the underlying problem (purulent bronchitis in the child with CF or ciliary dyskinesia, exacerbation of asthma). In the first two situations, it may not matter because treatment is the same. In the case of the child with asthma, it is important to treat the asthma with bronchodilating and antiinflammatory agents, as well as to treat the infected sinuses with antibiotics.

The treatment of sinusitis involves the use of oral antibiotics active against the common pathogens (Streptococcus pneumoniae, nontypable H. influenzae, Moraxella catarrhalis, and, in rare cases, anaerobic bacteria or Streptococcus pyogenes). Treatment regimens include the use of amoxicillin, amoxicillin-clavulanate, cefuroxime, cefpodoxime, or cefdinir. Amoxicillin is considered the initial agent of choice. Oral (pseudoephedrine, phenylephrine) or topical (phenylephrine, oxymetazoline) decongestants may be of benefit by increasing the patency of the sinus ostia, which permits drainage of the infected and obstructed sinuses. Oral antihistamines may benefit patients with an allergic history. Treatment with antimicrobial agents should continue for at least 7 days after the patient has responded. This may require 14 to 21 days of therapy. Many patients with presumed sinusitis recover without antibiotic therapy. Complications of acute sinusitis include orbital cellulitis, abscesses (orbital, cerebral), cranial (frontal) osteomyelitis (Pott puffy tumor), empyema (subdural, epidural), and thrombosis (sagittal or cavernous sinus).

See previous text and Chapter 5.

Viral Pneumonia. The features discussed for viral pneumonia in infants are relevant for viral pneumonia in older children. The differentiation of viral or atypical pneumonia from classical bacterial pneumonia is noted in Table 2 -11. Bacterial Pneumonia. Bacterial pneumonia is more common in toddlers and older children than in infants. The most common pathogen is S. pneumoniae; other bacterial causes vary with age ( Table 2-12) . Cough may not be as prominent a presenting symptom or sign as tachypnea and grunting, sometimes (especially in infants) with vomiting (see Table 2 -11). Raised respiratory rates (≥50 in infants 2 to 12 months old, ≥40 in children 1 to 5 years old) plus retractions and grunting with or without hypoxia (oxygen saturation <90%) have a high specificity and sensitivity for pneumonia. Chest pain, abdominal pain, headache, or any combination of these symptoms may occur. Upper lobe pneumonia may produce meningeal signs, and lower lobe involvement may cause abdominal pain and an ileus.

Examination of the chest shows tachypnea but may be otherwise surprisingly normal. In older children, there may be localized dullness to percussion, with crackles or amphoric (bronchial) breath sounds over a consolidated lobe. The chest film may be normal in the first hours of the illness, inasmuch as the radiographic findings often lag behind the clinical manifestations. Nonetheless, both posteroanterior and lateral views are the main diagnostic tools; lobar consolidation is usual, with or without pleural effusion. In infants, the pattern may be more diffuse and extensive.

Some clinical and radiographic features may be suggestive of the bacterial cause of pneumonia. Children (especially infants) with staphylococcal pneumonia are more likely to have a rapid overwhelming course. Staphylococcal pneumonia may be accompanied by more extensive radiographic abnormalities, including multilobar consolidation, pneumatocele formation, and extensive pleural (empyema) fluid. The presence of a pleural effusion is not helpful in indicating the specific bacterial diagnosis because other bacterial pneumonias may be accompanied by pleural effusion. Pleural effusions may represent a reactive parapneumonic effusion or an empyema. Pleural fluid may be characterized as transudate, exudate, or complicated empyema, the latter necessitating closed chest drainage with a chest tube (Table 2-13). If the effusion is of sufficient size, as demonstrated by a lateral decubitus film or ultrasonography, a thoracentesis is indicated to differentiate the nature of the effusion and to identify possible pathogens.

Differentiating among the causes of bacterial pneumonia can be done with certainty only with positive cultures from blood, pleural fluid, fluid obtained by direct lung tap, or, in rare cases, sputum. Current or previous antibiotic treatment diminishes the yield of such cultures. The presence of bacterial antigens in the urine for S. pneumoniae or H. influenzae provides strong evidence of the causative agent. Bronchoscopy with or without lavage may yield helpful specimens from the progressively ill child or the child who has not responded promptly to empirical antibiotics.

Treatment is with antibiotics. Cefotaxime or ceftriaxone is the drug of choice for the previously healthy child who requires hospitalization with lobar pneumonia. For the critically ill child, vancomycin may be considered for possible resistant S. pneumoniae. Many children with pneumonia do well with oral antibiotics (amoxicillin, amoxicillin-clavulanate, oral cephalosporins) and respond within hours to the first dose. A smaller number may require hospitalization and intravenous antibiotics along with supportive measures (e.g., oxygen and intravenous fluids). Repeated or follow-up chest films may remain abnormal for 4 to 6 weeks after pneumonia and are not indicated for a single episode of uncomplicated pneumonia (i.e., no effusion, no abscess, and good response to treatment). Children with suspected pneumococcal pneumonia must be monitored carefully because of the possibility of resistance to penicillin and cephalosporin.

Mycoplasma pneumoniae is a common cause of pneumonia among school-aged children. The disease often occurs in community outbreaks in the fall months. The illness typically begins with Table 2 -11); atypical in terms of extrapulmonary manifestations, low-grade fever, patchy diffuse infiltrates, poor response to penicillin-type antibiotics, and negative sputum Gram stain.

SARS, severe acute respiratory syndrome. extrapulmonary symptoms (i.e., sore throat, myalgias, headache, fever), which then progress to include worsening cough, paroxysmal at times. Patients do not often appear acutely ill, but cough may persist for weeks. There may be no specific abnormalities on the chest examination, although a few crackles may be heard, and about one third of younger patients wheeze.

The radiographic findings in mycoplasmal pneumonia can mimic almost any intrathoracic disease; scattered infiltrates with nonspecific "dirty" lung fields, predominantly perihilar or lower lobes, are common, and lobar infiltrates and pleural effusion are occasionally seen. Laboratory data (complete blood cell count, ESR, sputum culture) may not be helpful. A rise in antimycoplasmal immunoglobulin G over 1 to 2 weeks may be demonstrated but is seldom helpful in guiding therapy. A positive immunoglobulin M response may be useful, although it can persist in serum for several months and, consequently, may not indicate current infection. PCR may be helpful. The cold agglutinin test yields positive results in about 70% of patients with mycoplasmal pneumonia, but they are also positive in other conditions, including adenovirus infection. The more severe the illness is, the greater is the frequency of positive cold agglutinins. The diagnosis is often made from the history of an older child who has a lingering coughing illness in the setting of a community outbreak, unresponsive to most (non-erythromycin) antibiotic regimens.

Treatment is with erythromycin (azithromycin or clarithromycin are alternatives in children younger than 8 years, whereas tetracycline or doxycycline can be administered to older children), which usually shortens the course of the illness. Extrapulmonary complications of mycoplasmal infection include aseptic meningitis, transverse myelitis, peripheral neuropathy, erythema multiforme, myocarditis, pericarditis, hemolytic anemia, and bullous otitis media (myringitis). In patients with sickle cell anemia, severe respiratory failure and acute chest syndrome may develop. Infection with Chlamydia pneumoniae mimics respiratory disease resulting from M. pneumoniae, inasmuch as it occurs in epidemics, is seen in older children, and produces an atypical pneumonia syndrome and pharyngitis.

The incidence of tuberculosis is increasing as a result of acquired immunodeficiency syndrome, homelessness, urban poverty, and immigration from endemic countries. Tuberculosis must be considered in the child with chest disease that is not easily explained by other diagnoses, especially if the child has been exposed to an adult with active tuberculosis. Nonetheless, tuberculosis is an infrequent cause of cough in children, even in those with active disease.

The diagnosis is made primarily by skin testing (purified protein derivative [PPD]); a history of contact with a person who has tuberculosis; and recovery of the organism from sputum, bronchoalveolar lavage, pleural fluid or biopsy, or morning gastric aspirates (Table 2-14). The yield from these procedures is relatively low, even from children with active pulmonary tuberculosis.

The patterns of disease in normal hosts include primary pulmonary tuberculosis, with subsequent inactivation usually noted in young children and reactivation pulmonary disease among adolescents. Primary pulmonary disease is often noted as a lower or middle lobe infiltrate during the period of T lymphocyte reaction to the initial infection. Before resolution, the Mycobacterium tuberculosis infection may disseminate to the better oxygenated upper lobes and extrathoracic sites, such as bone, or the central nervous system. If the immune response contains the initial infection, the radiographic findings may be indistinguishable from those of any other pneumonic process. With altered immune function, however, there may be progressive local disease, dissemination to miliary pulmonary disease, or early reactivation (months to 5 years) at distal sites, which produces tuberculous meningitis or osteomyelitis. Reactivation of upper lobe pulmonary disease may produce cavities that are similar to the disease among adults. Cavitary and endobronchial lymph node involvement are highly infectious, in contrast to the much less contagious nature of the hypersensitivity reaction noted in primary pulmonary disease. Treatment of active disease, especially in regions of multidrugresistant tuberculosis, consists of three or four drug regimens, including isoniazid, rifampin, pyrazinamide with or without streptomycin, and ethambutol. Risk of infection based on history and PPD induration size are presented in Table 2 -14.

Inhaling food, mouth or gastric secretions, or foreign bodies into the tracheobronchial tree causes acute, recurrent, or chronic cough. Interference with normal swallowing disrupts the coordination of swallowing and breathing that prevents aspiration. Structural causes of disordered swallowing include esophageal atresia (in neonates), strictures, webs, or congenital stenoses. Mediastinal lesions (tumors, lymph nodes), including vascular rings, may compromise the esophageal lumen and esophageal peristalsis, increasing the likelihood of aspiration. Functional disorders include central nervous system dysfunction (e.g., coma, myopathy, neuropathy) or immaturity, dysautonomia, achalasia, and diffuse esophageal spasm. Prior neck surgery, including tracheostomy, may alter normal swallowing. Tracheoesophageal fistula and laryngeal clefts are congenital malformations with direct physical connections between the tracheobronchial tree and the upper gastrointestinal tract; oral contents enter the lungs directly.

Making the diagnosis of aspiration as the cause of cough may be difficult. Barium contrast studies during swallowing may help characterize these disorders if barium enters the trachea. Because most patients aspirate sporadically, a normal barium swallow does not rule out aspiration. Radionuclide studies can be helpful if ingested radiolabeled milk or formula is demonstrated over the lung fields at several-hour intervals after the meal. Bronchoscopy and bronchoalveolar lavage that recover large numbers of lipid-laden macrophages suggest that milk aspiration has taken place; however, the finding is neither sensitive nor specific for aspiration.

Treatment depends largely on the cause of aspiration. Because many patients who aspirate do so because of lack of neurologic control of swallowing and breathing, it is often difficult to prevent. Even gastrostomy feedings cannot prevent aspiration of oral secretions. In extreme cases, tracheostomy with ligation of the proximal trachea has been employed. This prevents aspiration but also prevents phonation, and it must be considered only in unusual situations. Aspiration pneumonia is often treated with intravenous penicillin or, preferably, clindamycin to cover mouth flora of predominant anaerobes. Additional coverage against gram-negative organisms (an aminoglycoside or cefepime) may be indicated if the aspiration is nosocomial.

Any child with cough of abrupt onset should be suspected of having inhaled a foreign body into the airway. Toddlers, who by nature put all types of things into their mouths and who have incompletely matured swallowing and airway protective mechanisms, are at high risk. Infants with toddlers or young children in the household who may "feed" the baby are also at risk. In older children, it is usually possible to obtain an accurate history of the aspiration event. These events are described as choking, gagging, and coughing while something (e.g., peanuts, popcorn, small toys, sunflower seeds) is in the mouth. The child may come to the physician with cough and wheeze immediately after the event, with a clear history and a straightforward diagnosis. In many children with a tracheobronchial foreign body, however, the initial episode is not recognized; these children may not come to medical attention for days, weeks, or even months (Fig. 2-9 ). The initial episode may be followed by a relatively symptomless period lasting days or even weeks, until infection develops behind an obstructed segmental or lobar bronchus. At this point, cough, perhaps with hemoptysis, with or without wheeze, recurs.

On physical examination early after an aspiration episode, there is cough, wheeze, or both, often with asymmetry of auscultatory findings. There may be locally diminished breath sounds. Later, localized wheeze or crackles may be detected. In some cases, the two-headed stethoscope may enable the examiner to recognize that a lobe or lung has delayed air entry or exit in comparison with the other side. The triad of wheezing, coughing, and decreased breath sounds is present in fewer than 50% of patients. The presence of laryngotracheal foreign bodies often manifests with stridor, retractions, aphonia, cough, and normal radiographs.

Chest radiographs may be normal in 15% of patients with intrathoracic foreign bodies but should be obtained in both inspiration and expiration, because in some cases the only abnormality is unilateral or unilobar air trapping, which is occasionally more clearly identified with a view in expiration. In this view, an overdistended lung that had appeared normal on the inspiratory view does not empty, but the normal, unobstructed lung empties normally. This phenomenon causes a shift of the mediastinum toward the emptying lung (away from the side with the obstructing foreign body). In other patients, localized infiltrate or atelectasis may be present behind the obstructing object. In a few patients, it may be possible to identify the foreign body itself; nonetheless, most inhaled food particles are not radiopaque and cannot be seen on radiographs. Aspiration is usually unilateral (80%); 50% to 60% of the objects are in the right lung (the lobe depends on body position-supine versus standing-but is often the right middle lobe). The definitive diagnostic and therapeutic maneuver is bronchoscopy; either the flexible or rigid open-tube bronchoscope enables direct visualization of the object; the rigid instrument also enables its removal.

GER is a common cause of cough in all age groups (see Chapter 16). The typical patient is an infant in the first 6 months of life who spits up small amounts of milk frequently after feedings. This "regurgitant reflux" most commonly resolves by 1 year of age. However, many toddlers and children continue to have reflux, although it may be "silent" or nonregurgitant (without spitting up). In most people with GER, it is merely a nuisance or not noticed. In some there are sequelae, and this condition is designated gastroesophageal reflux disease (GERD). One manifestation is cough; the mechanisms for the cough are not fully understood. Aspiration of refluxed material is one mechanism for cough but is probably not very common in neurologically intact children. A major mechanism for GERD with cough is mediated by vagal esophagobronchial reflexes (bronchoconstriction), stimulated by acid in the esophagus. Whether acid in the esophagus is sufficient stimulus to cause bronchoconstriction by itself or whether it merely heightens bronchial reactivity to other stimuli is not yet clear (see Chapter 3). Many children with reactive airways disease have cough or wheeze that is difficult to control until their concurrent GER is also treated. Many episodes of cough caused by GERD occur in children with asthma that is difficult to control.

The diagnosis of GERD must also be considered in the child with chronic or recurrent cough with no other obvious explanation. The child who coughs after meals or at night, when the supine position may provoke GER, should be evaluated for GER. If GER is confirmed, the next step is a therapeutic trial of antireflux therapy (see Chapter 16). If the results of the therapeutic trial are negative or equivocal, it may make sense to establish a causal relationship between the GER and the cough, by using the modified Bernstein test. During this test, hydrochloric acid and saline are alternately infused into the esophagus through a nasoesophageal tube while the child is observed for cough or wheeze or while the older child undergoes serial pulmonary function tests. If the symptoms occur or if pulmonary function deteriorates during acid but not saline infusion, it is likely that esophageal acidification through GER is the cause of the child's cough or wheeze.

Treatment in a child whose cough is related to GER may be accomplished by treating the reflux (see Chapter 16) or by a combination of antireflux and antiasthma treatment (see Chapter 3). Theophylline may worsen GER by lowering the tone of the lower esophageal sphincter, and some drugs that increase lower esophageal sphincter tone may cause bronchoconstriction. On occasion, the cough may be abolished by stopping all antiasthma medications. In such cases, the cough was a manifestation of reactive airways with esophageal acidification as the trigger for bronchospasm; the esophageal acidification was caused by the bronchodilator effects on the lower esophageal sphincter. Inhaled bronchodilators are less likely than oral or intravenous drugs to cause GER.

Cough is frequently the sole or most prominent manifestation of asthma; wheezing may be entirely absent. In fact, reactive airway disease or asthma (see Chapter 3) is almost certainly the most common cause of recurrent and chronic cough in childhood. Some of the features that characterize the cough of a child with asthma are listed in Table 2 -15. Treatment for asthma manifesting as cough is the same as the treatment for asthma (see Chapter 3).

CF is a common cause of recurrent or chronic cough in infancy and childhood. CF occurs in 1 in 2500 live births among white persons, is far less common among African Americans (1 in 17,000), and is rare among Native Americans and Asians. Early diagnosis improves the poor prognosis for untreated CF; if untreated, many patients die in infancy or early childhood. With current state-of-the-art care, median length of survival is to age 31.

CF is a genetic disorder, inherited as an autosomal recessive trait. The CF gene is on the long arm of chromosome 7; more than 1000 mutations have been identified at the CF locus. Of these mutations, one (ΔF508, indicating a deletion, Δ, of a single phenylalanine, F, at position 508 of the protein product) is the most common, responsible for 70% to 75% of all CF chromosomes. The currently recognized mutations account for approximately 90% of cases. The mutation affects the gene's protein product, termed cystic fibrosis transmembrane regulator, which acts as a chloride channel and affects other aspects of membrane transport of ions and water. Not all the consequences of the defective gene and protein have been determined. Most explain the long-observed clinical manifestations of the disease, including thick, viscid mucus in the tracheobronchial tree, leading to purulent bronchiolitis and bronchitis with subsequent bronchiectasis, pulmonary fibrosis, and respiratory failure; pancreatic duct obstruction, leading to pancreatic insufficiency with steatorrhea and failure to thrive; and abnormally high sweat chloride and sodium concentrations. The airway disease in CF is characterized by infection, inflammation, and endobronchial obstruction. The infection begins with S. aureus, H. influenzae, Escherichia coli, Klebsiella species, or combinations of these organisms but eventually is dominated by nonmucoid or mucoid Pseudomonas aeruginosa. Other organisms, such as Burkholderia cepacia, Xanthomonas maltophilia, Alcaligenes xylosoxidans, Aspergillus fumigatus, or nontuberculous mycobacteria may also appear; their significance remains undetermined. In some patients, B. cepacia has been associated with rapid deterioration and death, and in others, Aspergillus species has caused allergic bronchopulmonary aspergillosis. The airway inflammation in all patients with CF appears to be the result of toxic substances, including elastase, released by neutrophils as they respond to the endobronchial infection and by similar enzymes released by the invading organisms.

CF may manifest at birth with meconium ileus (10% to 15% of patients) or later, with steatorrhea and failure to thrive despite a voracious appetite, in an apparent effort to make up for the calories that are lost in the stool (see Chapter 15). The most common presenting symptom is cough, which may appear within the first weeks of life or may be delayed for decades. The cough can be dry, productive, or paroxysmal. Cough may respond to antibiotics or perhaps steroids, but it is less likely to improve with bronchodilators (see Tables 2-3 and 2-5). Although CF is a genetic disease, there is often no family history. Furthermore, in atypical cases, patients may not have pancreatic insufficiency (usually present in 85% to 90%) and thus may not demonstrate steatorrhea and failure to thrive. In addition, malabsorption may not be evident in the neonatal period.

There is no such thing as a child who looks "too good" to have CF; common abnormalities found on physical examination are noted in Table 2 -16. One of the most important physical findings is digital clubbing. In most patients with CF, clubbing develops within the first few years of life. Although the list of conditions associated with digital clubbing (Table 2-17) is long, they are less common than CF, or the incidence of digital clubbing with these conditions is low. There is some relationship between the degree of pulmonary disease severity and the degree of digital clubbing. A child who has had years of severe respiratory symptoms without digital clubbing is not likely to have CF. The diagnosis is confirmed by a positive sweat test or confirming the presence of two CF mutations on chromosome 7. The sweat test, if not performed correctly in a laboratory with extensive experience with the technique (as, for example, in an accredited CF center), yields many false-positive and false-negative results. The proper technique is to use the Gibson-Cooke method, with quantitative analysis of the concentration of sodium, chloride, or both, in the sweat produced after pilocarpine iontophoretic stimulation. Chloride (and sodium) concentrations higher than 60 mEq/L are considered positive indications, and those lower than 40 mEq/L are negative (normal). Healthy adults have slightly higher sweat chloride concentrations than do children, but the same guidelines hold for positive tests in adults. The non-CF conditions yielding elevated sweat chloride concentrations are listed in Table 2 -18. False-negative results of sweat tests can be seen in CF children presenting with edema or hypoproteinemia and in samples from children with an inadequate sweat rate. Sweat testing can be performed at any age; newborns within the first few weeks of life may not produce a large enough volume of sweat to analyze (75 mg minimum), but in those who do (the majority), the results are accurate. Indications for sweat testing are noted in Table 2-19. In patients for whom sweat testing is difficult (e.g., because of distance from an experienced laboratory, small infants who have not produced enough sweat, patients with extreme dermatitis, or patients with intermediate-range sweat chloride concentrations), DNA testing can be useful. Demonstration of two known CF mutations confirms the diagnosis. Finding one or no known mutation makes the diagnosis less likely but is not exclusive, inasmuch as there are patients with not-yet-characterized mutations. Furthermore, commercial laboratories do not identify all of the 1000-plus mutations.

Recovery of mucoid P. aeruginosa from respiratory tract secretions is strongly suggestive of CF. Similarly, pansinusitis is nearly universal among CF patients but is quite uncommon in other children. Some states are using a neonatal screen for CF. The CF screen is for immunoreactive trypsinogen (IRT) levels, which are elevated in most infants with CF for the first several weeks of life. (Some states do genetic testing on DNA.) Because of the very high sensitivity of this test (almost no one with CF has normal IRT levels) and because early institution of treatment is beneficial, this test may come into wider use. Its main drawback is that it has relatively poor specificity; as many as 90% of the positive results on the initial screen are false-positive results. If an infant's IRT screen is positive, the test should be repeated; at 2 to 3 weeks of age, which is when the test is repeated, the false-positive rate has fallen dramatically but is still quite high (25%). Definitive testing needs to be carried out on infants with two elevated IRT levels. In the unusual older child whose appendix is removed and examined carefully by a knowledgeable pathologist, the diagnosis may be suggested by the typical histologic appearance of the appendix (the mucus-secreting glands are overdistended with eosinophilic material). Laboratory data that may support the diagnosis of CF include absence of stool trypsin or chymotrypsin. This suggests pancreatic insufficiency, which occurs most commonly in CF but can be seen in other diseases. The test is not perfect even for confirming pancreatic insufficiency, because intestinal flora may produce or destroy trypsin. Pulmonary function test findings with an obstructive pattern, incompletely responsive to bronchodilators, are consistent with CF but, of course, can be seen in other conditions. Conversely, some patients with CF also have asthma and may show a marked response to a bronchodilator. Complications of CF that should suggest the diagnosis are noted in Table 2 -20.

The treatment of patients with CF requires a comprehensive approach, best performed in, or in conjunction with, an approved CF center. Several studies have shown survival to be significantly better in center-based care than in non-center-based care.

The treatment of the pulmonary aspects of CF involves approaching the obstruction, infection, and inflammation that cause the cough. Cough should be monitored closely, and any increase in frequency or in the intensity should be taken as an indication that there is worsening endobronchial infection, inflammation, or both. Because active infection and inflammation lead to irreversible lung damage, such changes need to be taken seriously and treated aggressively. This is just as true for the appearance of a mild morning cough in the child who was previously cough free as it is for severe coughing spells that keep a child awake through the night.

Obstruction is treated with physical means (chest physical therapy, with percussion, vibration, and postural drainage) to dislodge the mucus into the large central airways, where cough can then effectively clear it. Studies have shown this rather crude and timeconsuming procedure to be effective in helping to maintain lung function acutely and over a period of years. Variations on the physical maneuvers to help with mucus clearance include forced expiratory technique, positive airway pressure face masks, and masks with expiratory flutter valves. The frequency with which any of these physical means of expelling mucus should be used varies but should be increased with signs of active infection and obstruction.

Other approaches to relieving obstruction in the bronchial tree include the use of inhaled bronchodilators (despite a paucity of studies showing their long-term efficacy) and mucolytic agents. N-acetylcysteine (Mucomyst) has been available for years, but it may cause tracheobronchial irritation, with bronchorrhea, bronchospasm, or both, in an unacceptably high proportion of patients. An inhaled drug, dornase alfa, or recombinant human DNase (Pulmozyme), is clearly effective in the test tube for liquefying the thick mucus associated with CF. This occurs because 40% of the mucus viscosity in CF is attributed to DNA released from dying polymorphonuclear cells. Another drug that appears promising is amiloride. Long available as a diuretic, amiloride can bring about a partial correction of the membrane transport defects in CF. Amiloride aerosols seem to decrease sputum viscosity and increase cough clearance. In a small 6-month study, aerosolized amiloride appeared to slow the decline in lung function.

The approach to endobronchial infection in children with CF includes prevention and treatment. Prevention involves immunizing patients with CF against preventable respiratory pathogens, particularly influenza, measles, and pertussis. Prevention also means avoiding unnecessary exposure to respiratory viruses (e.g., at day care centers). It should not mean avoiding school or other social functions and settings, because this approach is invariably futile and can cause severe emotional damage. However, spread of bacteria, especially resistant organisms such as B. cepacia, between patients is a concern.

Treatment of infection usually proceeds in a stepwise manner. If colonies of H. influenzae or S. aureus are present, appropriate antibiotics should be initiated. If no recent throat or sputum specimens for culture are available, and if the patient is young with very mild lung disease, empirical therapy can also be directed at those organisms. In the older or sicker patient who has any sign of chronic pulmonary involvement, such as pulmonary overinflation, infiltrates on a chest film, digital clubbing, or severe coughing spells, it makes sense to include antibiotics effective against P. aeruginosa (Fig. 2-10 ; Table 2 -21) .

Treatment of the inflammation associated with CF is evolving. Some patients benefit from short-term oral prednisone. A 4-year study of alternate-day prednisone showed improved pulmonary function but unacceptable side effects (e.g., glucose intolerance, growth failure) in those taking 2 mg/kg/day and similar side effects (although less severe) in those taking 1 mg/kg/day. The beneficial role of oral nonsteroidal antiinflammatory agents has been demonstrated; the role of inhaled topical steroids and α1-antitrypsin is being investigated. Table 2 -22 lists the main anatomic abnormalities (most of them congenital) that cause cough.

Vascular rings and slings are often associated with inspiratory stridor because the abnormal vessels compress central airways, most commonly the trachea (see Chapter 5). The patient may also have difficulty swallowing if the esophagus is compressed.

The diagnosis may be suspected from plain films of the chest, especially those showing tracheal deviation and a right-sided aortic arch. Further support for the diagnosis can be found at bronchoscopy (which shows extrinsic compression of the trachea or a mainstem bronchus), barium swallow study (which shows esophageal compression), or both. The definitive diagnosis is made with magnetic resonance imaging, angiography, or magnetic resonance angiography. Treatment is surgical.

Pulmonary sequestration is relatively unusual, occurring in 1 in 60,000 children. It occurs most commonly in the left lower lobe and can manifest in several ways (Fig. 2-11 ; see Table 2 -22) . The chest radiograph usually shows a density in the left lower lobe; this density often appears to contain cysts. The feature distinguishing a sequestered lobe from a complicated pneumonia is that the blood supply arises from the aorta and not the pulmonary circulation. Doppler ultrasonography and angiography provide the definitive diagnosis. The treatment is surgical removal.

Cystic adenomatoid malformation is a rare condition. It manifests in infancy with respiratory distress in nearly 50% of cases; the other half may manifest as cough with recurrent infection later in childhood or even adulthood. The chest film reveals multiple cysts, separated by dense areas. Chest CT scans can help make the diagnosis with near certainty. Surgical removal is the treatment. 

Congenital lobar emphysema occurs in one of 50,000 live births. It can manifest dramatically with respiratory distress in the neonatal period or later (Fig. 2-12) , with cough or wheeze, or as an incidental finding on a chest radiograph. Radiography shows localized overinflation, often dramatic, with compression of adjacent lung tissue and occasionally atelectasis of the contralateral lung because of mediastinal shift away from the involved side. The appearance on chest CT scan is typical, with widely spaced blood vessels (as opposed to congenital cysts, for example, which have no blood vessels within the overinflated area). Bronchoscopy can document patent bronchi and should probably be performed in older children, in whom congenital lobar emphysema can be confused with acquired overinflation of a lobe as the result of bronchial obstruction, as with a foreign body. If the disease is symptomatic, treatment is surgical.

Tracheoesophageal fistula is common, with an incidence of about one in 5000 live births. Of these fistulas, the large majority (85%) are associated with esophageal atresia; only 3% are the isolated, H-type fistula (a patent esophagus with fistulous tract connecting the esophagus and trachea). A neonate with esophageal atresia experiences respiratory distress, excessive drooling, and choking and gagging with feeding. The H-type fistula causes more subtle signs and may be undiagnosed for months or even years. The child may have only The diagnosis is not challenging in the infant with esophageal atresia; a nasogastric tube cannot be passed, and swallowed barium outlines the trachea. In the older child with H-type fistula, a barium esophagogram may or may not reveal the fistula. Bronchoscopy and esophagoscopy should permit direct visualization of the fistula; however, the opening may be hidden in mucosal folds.

Treatment is surgical. Many children born with tracheoesophageal fistula have recurrent cough and lower respiratory tract infection for many years, even after successful surgical correction. The cough is characteristically the harsh cough of tracheomalacia, which is present at the site of the fistula. The infections result from several causes, including GER, with or without aspiration, and altered mucociliary transport. Treatment involves regular chest physical therapy and early and aggressive use of antibiotics whenever there is evidence of increased pulmonary symptoms.

Hemangiomas may be present within the airway and can cause cough, rarely with hemoptysis; stridor (if the hemangioma is high in the airway) and respiratory distress (if the hemangioma is large) may also occur. In rare cases, with very large airway hemangiomas, there may even be dysphagia from extrinsic compression. About 50% of children with airway hemangiomas have cutaneous hemangiomas as well.

The diagnosis is made with bronchoscopy. As with cutaneous hemangiomas, these lesions may resolve spontaneously over the first year or so. However, if they cause symptoms, it may not be advisable or possible to wait for them to resolve.

Many airway hemangiomas regress with steroid treatment, although others have been shown to respond to interferon-α. Laser ablation may be indicated in some refractory cases. In the case of a large subglottic hemangioma, a tracheostomy is frequently performed and maintained until the mass regresses.

Enlarged mediastinal lymph nodes, such as those resulting from tuberculosis, leukemia, other hematologic malignancies, or other infections, are occasionally a cause of cough in children (Tables 2-22 and 2-23). These nodes are usually seen on plain films of the chest. The x-ray study or bronchoscopy may show extrinsic compression of the trachea. Treatment is directed at the underlying cause.

Occasionally bronchial stenosis, either congenital or acquired, may cause cough. The diagnosis is made with bronchoscopy, after suspicion has been raised by the child's having recurrent infiltrates in the same lobe, especially with localized wheeze.

Treatment may be difficult. In some cases, endoscopic balloon dilatation or airway stent placement is successful; in others, surgical resection of stenotic areas may be necessary.

Bronchogenic cysts are uncommon, but they can cause cough, wheeze, stridor, or any combination of these. They may also cause recurrent or persistent pneumonia if they block a bronchus sufficiently to interfere with normal drainage of the segment or lobe. Radiography may show localized overinflation if the cyst causes a ball-valve-type obstruction. The cyst itself may or may not be seen on plain films. Bronchoscopy reveals extrinsic compression of the airway. CT studies often definitively show the lesion. Surgical removal is indicated.

On occasion, a school-aged child may develop a cough that lasts for weeks, often after a fairly typical cold. This cough occurs only during wakefulness, never during sleep. In many cases, the cough is harsh and foghorn-like. It often disrupts the classroom, and the child is asked to leave. The child is otherwise well and may seem rather unbothered by the spectacle created. There has been no response to medications. It seems that this type of cough, often termed "psychogenic," or "psychogenic cough tic," but perhaps more accurately and humanely thought of as habit cough, has given the child valuable attention. This attention then serves as the sustaining force, and the cough persists beyond the original airway inflammation. In the small minority of cases, there may be deep-seated emotional problems, of which the cough is the physical expression.

During the history or physical examination, the child appears completely well and may cough when attention is drawn to the child or when the word "cough" is uttered. The physical examination findings are otherwise completely normal, as are laboratory values. Because this may occur in any child, evidence of mild reactive airways disease (history or pulmonary function testing) does not rule out the diagnosis. Once a physician has seen a child with this problem, it is usually possible to make the diagnosis with certainty on entering the examining room or, indeed, from the hallway outside the room.

Treatment can prove more difficult. There are several treatment schools, summarized in Tables 2-24 and 2-25. One approach is "the bed sheet," in which the child is told that he or she coughs because of weak chest muscles. A bed sheet is wrapped tightly and uncomfortably around the chest "to serve as added support for the muscles … [and] with this support, the muscles would then be able to suppress [the] cough." The child is to go to school wearing the bulky bed sheet under his or her clothes and may not remove the sheet until he or she is certain that the cough will not return. The authors who describe this method call it a "reinforcement suggestion technique." Some view this approach as demeaning to the child. Whatever its mechanism of action, this method was reported to have been successful in 31 of 33 patients. 

Postnasal drip is thought to be a major cause of cough in adults. The mechanism by which this occurs is unclear, and most pulmonologists believe that this must remain a diagnosis of exclusion for explaining cough in children.

Bronchiectasis is defined as an abnormal dilation of the subsegmental bronchi and is usually associated with chronic cough and purulent sputum production. It occasionally occurs after severe pneumonias (bacterial or viral); it eventually develops in nearly all patients with CF. Diagnosis may, on occasion, be made with plain chest radiographs, but high-resolution CT scanning is the diagnostic procedure of choice, replacing bronchography. Treatment of bronchiectasis consists of chest physiotherapy and postural drainage, occasionally bronchodilators and mucolytic agents, and antibiotic therapy during exacerbations. Surgical resection may be indicated in cases that are progressive and localized when medical therapy has failed. The prognosis of bronchiectasis depends on the underlying cause. Bronchiectasis associated with CF is fatal, although many cases of bronchiectasis remain stable or may even regress with therapy.

Conditions in which the cilia do not function properly (dysmotile cilia or ciliary dyskinesia) lead to cough, usually because infection (and bronchiectasis) occurs in the absence of normal mucociliary transport. Treatment is similar to that for CF, with regular chest physical therapy and frequent and aggressive use of antibiotics at the first sign of airways infection, most commonly increased cough.

There are several varieties of interstitial lung disease: desquamative, lymphoid, and "usual" (see Chapter 3). All are very uncommon in childhood, and little is known about their causes, courses, or treatment. One type of pediatric interstitial lung disease, the lymphoid type, is becoming much more common, inasmuch as it is seen in human immunodeficiency virus (HIV) infection. Interstitial lung disease manifests with cough, dyspnea, and crackles on examination. Because the diagnosis is based on histologic findings, lung biopsy is required. The only exception to this may be in the child with documented acquired immunodeficiency syndrome who has new pulmonary infiltrates and symptoms, in whom bronchoscopy and bronchoalveolar lavage are initially used to diagnose infection (P. carinii, cytomegalovirus).

Interstitial lung disease in a patient with a chronic seborrhea-like dermatitis should suggest the diagnosis of histiocytosis X.

Heart failure can cause cough but seldom as its sole clinical manifestation.

Pulmonary hemosiderosis is a rare, and often fatal, condition of bleeding into the lung that can manifest with cough. If sputum is produced, it is often frothy and blood-tinged. There may be frank hemoptysis. However, the cough may be nonproductive, or the sputum may be swallowed. Some cases are associated with milk Perform all possible tests Can tell patient and family: "We've Reinforces the idea of a physical cause ruled out all physical problems." In one study, resolution followed bronchoscopy ("aversive stimulus"?) Apply an aversive stimulus Has worked in some patients By definition, this treatment is unpleasant (e.g., an electric shock to forearm) Try the "bed sheet" (see text)

Seems to work in most patients Demeans the patient Try placebo drugs Probably works in some patients Is a dishonest technique Provide psychotherapy May work in some patients Is unnecessary in most patients; labels the patient as having a psychological problem Gently explain that there is no physical Works in some patients Is resented by some families focused on cause and this is a habit that the body an organic cause or treatment has sustained Prevent mouth breathing by holding a Has worked in some patients Not known button between the patient's lips Apply speech therapy techniques (see Works in many patients: can be presented Is resented by some families focused on Table 2-25) as specific therapy; nonthreatening organic cause or treatment Treatment is often unsatisfactory; the mortality rate is as high as 50%. Milk products should be eliminated from the patient's diet, and underlying collagen vascular disease should be treated. Some affected children seem to respond to corticosteroids or cytotoxic drugs (e.g., azathioprine, cyclophosphamide, and chlorambucil), but the episodic nature of the disease, with some clear cases of spontaneous resolution, makes it difficult to evaluate therapies.

See Chapter 3.

Tumors, which fortunately are rare in childhood, can cause cough, usually because of bronchial blockage, either extrinsic or endobronchial (see Table 2 -23). The diagnosis is usually made from bronchoscopy, chest CT, or both. Treatment depends on the cell type, but it usually involves at least some surgical removal. Chemotherapy or radiation may be used in some cases.

Isolated tracheomalacia or bronchomalacia is uncommon but can cause cough in some children. The cough of tracheomalacia is typically harsh and brassy. Treatment is difficult but, fortunately, is seldom needed.

Some children, usually preschoolers, may episodically awaken at night with stridor and a harsh, barking cough indistinguishable from that of viral croup. This entity is termed spasmodic croup and is of unclear origin. Viral and allergic causes have been postulated. GER may be the cause in some patients.

Treatment with cool mist or racemic epinephrine is effective in most patients. If GER is the underlying cause, antireflux treatment is beneficial.

Obliterative bronchiolitis is very rare except in lung transplant recipients. In other instances, it may arise after adenovirus, measles, or influenza pneumonia; after exposure to certain toxins; or in other rare circumstances. Children may exhibit cough, respiratory distress, and exercise intolerance.

The diagnosis is suggested by the pulmonary function or radiographic evidence of small airways obstruction; however, these findings are not always present. Not all chest films show overinflated lungs, and not all pulmonary function tests show decreased small airways function.

The definitive diagnosis is histologic via open or transbronchial biopsy. No specific treatment is available. Most children with obliterative bronchiolitis recover, but many progress to chronic disability or death.

The child who coughs out blood or bloody mucus presents special diagnostic and therapeutic challenges. Although hemoptysis is relatively uncommon in children, particularly among those without CF, many conditions can cause it (Table 2-27) . It is important (and not always easy) to distinguish cases in which blood has originated in the tracheobronchial tree (true hemoptysis), the nose (epistaxis), and the gastrointestinal tract (hematemesis). Table 2 -28 gives some guidelines to help localize sites of origin of blood that has been reported or suspected as hemoptysis. None of these is foolproof, partly because blood that has originated in one of these sites might well end in another before being expelled from the body; for instance, blood from the nose can be swallowed and vomited or aspirated and coughed out.

Infection is among the most common causes of hemoptysis. Lung abscess and tuberculosis need to be considered. Bronchiectasis can readily cause erosion into bronchial vessels, often made tortuous by years of local inflammation, and produce hemoptysis. Other infectious settings are less common and include necrotizing pneumonias and fungal and parasitic lung invasion.

Foreign bodies in the airway can cause hemoptysis by direct irritation, by erosion of airway mucosa, or by secondary infection.

Pulmonary embolus is uncommon in children and adolescents, but it needs to be considered in the differential diagnosis of an adolescent with hemoptysis of unclear origin. Clues to the diagnosis of pulmonary embolus include a positive family history, severe dyspnea, chest pain, hypoxia, a normal chest film, an accentuated second heart sound, an abnormal compression ultrasonographic study of the leg veins, a positive Homans sign, a positive helical CT scan, and a high-probability lung ventilation-perfusion scan.

The diagnosis of several causes of hemoptysis is straightforward. For example, hemoptysis that occurs immediately after a surgical or invasive diagnostic procedure in the chest should suggest an iatrogenic problem. The chest film can help suggest lung abscess, pulmonary Bronchoscopy can sometimes localize a bleeding site, identify a cause (e.g., a foreign body or endobronchial tumor), or recover an offending bacterial, fungal, or parasitic pathogen. In many instances, bronchoscopy does not help except by excluding some possibilities, because either no blood or blood throughout the tracheobronchial tree is found. Bronchial artery angiography may help to identify the involved vessel or vessels.

Treatment of hemoptysis depends on the underlying cause. It can be a terrifying symptom to children and their parents, and a calm, reassuring approach is essential. Because hemoptysis is seldom fatal in children, reassurance is usually warranted. Furthermore, hemoptysis most often resolves, and treatment of the bleeding itself is not often needed. What is required is treatment of the underlying cause of the hemoptysis, such as therapy for infection, removal of a foreign body, or control of collagen-vascular disease. When death occurs from hemoptysis, it is more likely to be from suffocation than from exsanguination. In cases of massive bleeding, the rigid open-tube bronchoscope may help suction large amounts of blood while ventilating and keeping unaffected portions of lung clear of blood. Interventional radiologists treat as well as localize a bleeding site by injecting the offending vessel with occlusive substances, such as Gelfoam or silicone coils. In extremely rare instances, emergency lobectomy may be indicated.

Cough itself seldom necessitates specific treatment. Nonetheless, cough is not always completely benign (see Table 2 -9). Most complications are uncommon, and most accompany only very severe cough, but some are serious enough to justify treatment of the cough itself.

Cough suppressants include codeine and hydrocodone (two narcotics) and dextromethorphan (a nonnarcotic D-isomer of the codeine analogue of levorphanol). Such agents should be used only for severe cough that may produce significant complications (see Table 2 -9). For most diseases, suppressing the cough offers no advantage. Disadvantages include narcotic addiction and loss of the protective cough reflex with subsequent mucus retention and possible superinfection. Demulcent preparations (sugar-containing, bland soothing agents) temporarily suppress the cough response from pharyngeal sources, and decongestant-antihistamine combinations may reduce postnasal drip and thus cough in adults. 

Evaluation of chronic or recurrent cough

The cough and the bedsheet

Managing cough as a defense mechanism and as a symptom. A consensus panel report of the American College of Chest Physicians

Bacterial tracheitis: Report of eight new cases and review

Computed tomographic study of the common cold

Epidemiology, pathogenesis, and treatment of the common cold

Does this patient have sinusitis? Diagnosing acute sinusitis by history and physical examination

Report of the Committee on Infectious Diseases

Chlamydial respiratory infections

Infant pneumonitis associated with cytomegalovirus, Chlamydia, Pneumocystis, and Ureaplasma: Follow-up

Value of radiological follow-up of childhood pneumonia

Etiology and treatment of pneumonia

Report of a workshop on respiratory viral infections: Epidemiology, diagnosis, treatment, and prevention

Pulmonary manifestations of acquired immunodeficiency syndrome

Standardized diagnosis of pneumonia in developing countries

The causes of hospital-treated acute lower respiratory tract infection in children

Hypoxaemia in young Kenyan children with acute lower respiratory infection

The evaluation of the child with recurrent chest infections

Bronchoscopic removal of aspirated foreign bodies in children

Tracheobronchial foreign bodies

Subglottic foreign bodies in pediatric patients

Tracheobronchial foreign bodies

Cystic Fibrosis

The cystic fibrosis genotype-phenotype consortium. Correlation between genotype and phenotype in patients with cystic fibrosis

Prospects for gene therapy in cystic fibrosis

Prediction of mortality in patients with cystic fibrosis

Wheezing in infants with cystic fibrosis: Clinical course, pulmonary function, and survival analysis

Physiotherapy in cystic fibrosis

Efficacy and safety of short-term administration of aerosolised recombinant human DNase I in adults with stable stage cystic fibrosis

The diagnosis of cystic fibrosis: A consensus statement

Emerging therapies for cystic fibrosis

Pseudomonas cepacia: Pulmonary infection in patients with cystic fibrosis

Effect of long-term treatment with inhaled budesonide on adult height in children with asthma

A clinical index to define risk of asthma in young children with recurrent wheezing

Airway responsiveness in early infancy predicts asthma, lung function, and respiratory symptoms by school age

Low-dose inhaled corticosteroids and the prevention of death from asthma

Third International Pediatric Consensus Statement on the Management of Childhood Asthma. International Pediatric Asthma Consensus Group

Venous thromboembolic complications in children

Clinical assessment and management of massive hemoptysis

Massive haemoptysis: Medical management will usually arrest the bleeding

Pathogenesis and management of hemoptysis in children

Cough is important because it is a symptom and sign of underlying disease that frequently merits treatment. In the acute setting, severe disease, including massive hemoptysis or profound dyspnea or hypoxemia, warrants immediate attention, rapid diagnosis, and rapid management. Certain chronic conditions, including those that suggest CF and those in which symptoms have persisted and interfere with a child's daily activities and quality of life, warrant further evaluation and treatment. Finally, a child whose cough fails to respond to what should have been reasonable treatment should be referred to a pulmonary specialist (Table 2-29) .