Infancy (Younger Than 1 Year)

Cough starting at birth or shortly afterward may be a sign of serious respiratory disease and must be evaluated assiduously. Cough beginning at this time raises the possibility of congenital infections, such as cytomegalovirus or rubella, which are often associated with other findings, such as hepatosplenomegaly, thrombocytopenia, or central nervous system disease. Pneumonia due to Chlamydia trachomatis (Fig. 16-7) generally develops after the first month of life and presents as an afebrile pneumonitis with congestion; wheezing; fine, diffuse crackles; a paroxysmal cough; and, in approximately 50% of cases, a prior or concomitant inclusion conjunctivitis. Pneumonia caused by Bordetella pertussis is a potentially life-threatening illness characterized by severe paroxysmal coughing episodes followed by cyanosis and apnea and is often associated with an inspiratory “whoop.” The latter finding may be missing in young infants or those weakened by the recurrent coughing spasms. Newborns and young infants may have apnea as the primary sign of a B. pertussis infection. The chest radiograph is nondiagnostic and can be normal or (Fig. 16-8) show perihilar infiltrates; atelectasis; hyperinflation; and, in some cases, interstitial or subcutaneous emphysema. A high white blood cell count with a predominance of lymphocytes supports the diagnosis, but unfortunately once the patient has passed through the usually innocent-appearing coryzal stage into the paroxysmal stage, diagnostic tests have a lower yield. Diagnostic approaches to whooping cough include detection of B. pertussis DNA by polymerase chain reaction (PCR) and serologic detection of B. pertussis–specific IgM or IgA. Ureaplasma urealyticum and Pneumocystis jirovecii (formerly known as P. carinii) have been recognized as causes of pneumonia and persistent cough in this age group.

Figure 16-7 Pneumonia caused by Chlamydia trachomatis in a 3-month-old infant with inclusion conjunctivitis.

Figure 16-8 Pertussis in a 6-week-old infant demonstrates the typical radiographic pattern of perihilar involvement. This child also has right upper lobe atelectasis.

(Courtesy Katie McPeak, MD, Pittsburgh, Pa.)

Congenital malformations, such as tracheoesophageal fistula (Fig. 16-9) and laryngeal cleft or web, can produce cough via chronic aspiration of gastric contents, milk, or saliva. These anomalies are associated with feeding-related coughing, choking, and occasional cyanosis. Hypoxemia may persist between feedings. Infants with neurologic disorders may have incoordination of swallowing and sucking reflexes that lead to aspiration of milk or gastric contents into the lung. Pulmonary sequestration (in which a portion of the lung is perfused by systemic, not pulmonary arteries) (Fig. 16-10) and bronchogenic cysts (cystic structures arising from the pulmonary epithelium) are rare congenital anomalies that may compress the pulmonary tree or become infected, thereby producing a cough. Aberrant major blood vessels generally cause inspiratory stridor and expiratory wheezing from tracheal compression (Fig. 16-11; see also Fig. 16-25), but a brassy cough may also be observed, as may dysphagia from the associated esophageal compression.

Figure 16-9 Tracheoesophageal fistula. A, Anteroposterior chest radiograph shows feeding tube passing no farther than proximal esophagus; there is an aspiration pneumonitis present. B, Lateral view showing the feeding tube in the proximal esophageal pouch with air in the airway, distal esophagus, and intestine.

(A, Courtesy Beverly Newman, MD, Pittsburgh, Pa; B, courtesy Katie McPeak, MD, Pittsburgh, Pa.)

Figure 16-10 Pulmonary sequestration. A, Anteroposterior film shows left lower lobe infiltrate. B, Aortic angiogram demonstrates anomalous origin of pulmonary blood supply from abdominal aorta to the left lower lobe in a 7-year-old girl with extralobar sequestration.

(Courtesy Geoffrey Kurland, MD, Pittsburgh, Pa.)

Figure 16-11 Vascular ring. Barium swallow in a toddler with posterior compression of esophagus and trachea from a vascular ring.

(Courtesy Department of Radiology, Children’s Hospital of Pittsburgh, Pittsburgh, Pa.)

The triad of poor weight gain, steatorrhea, and chronic cough at this age makes cystic fibrosis a strong consideration, and a sweat test at an accredited cystic fibrosis center is mandatory. Asthma (formerly: “reactive airway disease”) or bronchial hyperresponsiveness is a common and probably underdiagnosed cause of cough in infancy. Cough or persistent wheezing can be found in these infants, who may have a history of a previous viral lower respiratory illness with or without a family history of wheezing and/or asthma. Babies with GER may have a combination of effortless vomiting; nocturnal cough/wheeze; pain behaviors/arching; hoarseness; laryngomalacia; and, in some cases, poor weight gain. The absence of a history of vomiting (“spitting up”) does not eliminate GER as a diagnostic consideration in infants with persistent coughing because occult reflux or microaspiration may induce bronchospasm.

Childhood interstitial lung disease (chILD) refers to a complex and rare group of pulmonary disorders. These disorders usually involve the pulmonary interstitium, but can involve other aspects of lung parenchyma. Although chILD can present in older children, there are several disorders (see later) specific to infancy. The pathogenesis of these disorders is poorly understood.

Causes of chILD are extremely variable and include infections, inhalation injury, chemotherapeutic agents, post–bone marrow transplant lung disease, systemic inflammatory diseases, pulmonary hemorrhage syndromes, structural and growth anomalies, metabolic diseases, and congenital disorders of host defense and of surfactant production. Examples of chILD that present in infancy include alveolar capillary dysplasia, surfactant B and C deficiencies, ILD associated with ABCA3 mutations, pulmonary interstitial glycogenosis, neuroendocrine cell hyperplasia of infancy, and follicular bronchitis of infancy.

Patients with chILD may present insidiously with some combination of cough, tachypnea, retractions, exercise intolerance, resting hypoxemia or hypercarbia, or desaturation with exercise; diffuse abnormalities on chest imaging; and crackles and retractions on examination. Growth failure is not uncommon as a complication of these diseases.

The diagnosis of a specific chILD is usually made subsequent to lung biopsy, but this is usually preceded by a variety of less invasive tests (Fig. 16-12) such as a high-resolution computed tomography (CT) scan of the chest, infant lung function testing, and flexible fiberoptic bronchoscopy with bronchoalveolar lavage. Surfactant disorders (surfactant protein B or C deficiencies, or ABCA3 mutations) can often be diagnosed by mutation analysis. The prognosis of chILD can be quite variable, with some universally fatal (alveolar capillary dysplasia) or very severe and treatable only by lung transplantation (surfactant protein B deficiency), and some showing gradual improvement over months or years (neuroendocrine cell hyperplasia of infancy).

Figure 16-12 Computed tomography scan (A) and infant lung function testing (B) in a young child with neuroendocrine cell hyperplasia of infancy.

Preschool

The two most common reasons for a persistent cough in the preschool age group are recurrent viral infections and asthma. The child with asthma may not manifest audible wheezing or dyspnea but rather may have persistent cough, especially with viral respiratory infections, after exposure to noxious inhalants, such as cigarette smoke, or after vigorous activity.

Upper respiratory tract disease and sinusitis have been implicated in the pathogenesis of chronic cough, presumably through the stimulation of pharyngeal cough receptors by upper airway secretions. Parental smoking (passive smoking) itself is a common cause of cough in preschool children. GER more commonly causes cough at a younger age but may appear at any age. The interstitial pneumonitides may also produce a chronic cough in this age group.

An inhaled foreign body in either the tracheobronchial tree or esophagus is an important cause of chronic cough, especially in toddlers. A history of gagging or choking may be absent at this age, physical examination may be unrevealing, and the plain chest radiograph may be normal. Subtle differences in air entry into homologous lung segments, detected with the differential (double-headed) stethoscope (see Fig. 16-1), may be the only indication of a foreign body in the airway. Cough is present in more than 90% of cases; it is usually of abrupt onset, but a quiescent period may occur after inhalation and cough may disappear as irritant receptors adjust to the object’s presence. A mobile foreign body may result in the recurrence of cough as new receptors are stimulated by the object. Although inspiratory and expiratory radiography and fluoroscopy are useful in the evaluation of a child with a possible bronchial foreign body, they may be normal and rigid bronchoscopy may be necessary to confirm or disprove the presence of a foreign object (Fig. 16-13). Unilateral air trapping demonstrated by inspiratory and expiratory radiographs (Fig. 16-14, A and B) (or left and right lateral decubitus films in younger children) strongly suggests an inhaled foreign body.

Figure 16-13 Foreign body. Portion of a carrot lodged in the right mainstem bronchus, as seen through a rigid bronchoscope.

(Courtesy S. Stool, MD, Pittsburgh, Pa.)

Figure 16-14 Foreign body. Inspiratory (A) and expiratory (B) radiographs of a child with an inhaled foreign body lodged in the left mainstem bronchus reveal hyperlucency of the left hemithorax and compensatory shift of the mediastinal structures to the right on expiration.

(Courtesy Sameh Tadros, MD, Pittsburgh, Pa.)

Suppurative lung diseases, such as cystic fibrosis or bronchiectasis (Fig. 16-15), or deriving from any other causes (e.g., tuberculosis), characteristically result in a chronic cough producing purulent sputum. “Right middle lobe syndrome,” commonly associated with enlargement of lymph nodes surrounding the right middle lobe bronchus in tuberculosis, has also been described in asthma and a number of other illnesses and may be associated with chronic cough. Recurrent infection of the middle lobe can ultimately lead to the development of bronchiectasis or fibrosis.

Figure 16-15 Bronchiectasis. Bronchogram shows cylindrical bronchiectasis of the left lower lobe in a 5-year-old girl with recurrent pneumonia and chronic cough.

Disorders of ciliary motility (primary ciliary dyskinesia and acquired ciliary dyskinesia) may produce insidious symptoms of chronic productive cough, nasal drainage, recurrent middle ear infections, and fever. Clinical findings include basilar crackles (which can be expiratory) and, later, radiographic changes of recurrent lower lobe infections and bronchiectasis. Repetitive infections occur unless measures such as chest physical therapy, postural drainage, and liberal use of antibiotics are employed. It is now recognized that the classic triad described by Kartagener of situs inversus, sinusitis, and bronchiectasis fits only a limited number of patients because situs inversus occurs in only about half of all patients with primary cilia dyskinesia. Far more common is an acquired ciliary dyskinesia that can follow certain lower respiratory infections (including adenovirus, Mycoplasma, respiratory syncytial virus, and influenza). Diagnosis can be made via biopsy of the respiratory epithelium, either from curettage of the nasal turbinate in the office or from forceps biopsy of the bronchus via rigid bronchoscope under anesthesia. It may also be suggested by a reduced fraction of nitric oxide in exhalate from the nose.

Pulmonary hemosiderosis is a potentially fatal disorder that has been described in association with cardiac or panorganic disease, glomerulonephritis (Goodpasture syndrome), collagen vascular diseases, and as an idiopathic form. Idiopathic pulmonary hemosiderosis (IPH) is a disease of unknown etiology characterized by episodes of dyspnea, cough and/or hemoptysis, cyanosis, fever, and iron-deficiency anemia. Hematemesis or melena may be the only presenting complaint in some patients without symptoms referable to the respiratory tract. As a result of recurrent bleeding episodes, jaundice may be observed, and clubbing develops over time in some patients. Laboratory findings include iron-deficiency anemia and, in a small number of patients, peripheral eosinophilia. Radiographic findings are quite variable, with some patients demonstrating scant transient infiltrates and others showing widespread parenchymal infiltrates that resemble miliary tuberculosis. Hemosiderin-laden macrophages obtained from sputum, gastric washings, or bronchoalveolar lavage suggest the diagnosis, but a lung biopsy is frequently necessary and will allow the clinician to differentiate vasculitis from capillaritis and assess for iron deposition. A percutaneous renal biopsy or detection of anti–basement membrane antibodies may help in cases of hemosiderosis associated with Goodpasture syndrome.

School Age to Adolescence

Because children are exposed to numerous respiratory viruses during the first several years of school, recurrent viral infection remains an important cause of chronic cough in this age group. Asthma continues to be a consideration in the patient with a chronic cough. Patients in this age group (older than 6 years) can perform pulmonary function tests including bronchodilator responsiveness or bronchial provocation studies to confirm the diagnosis. Other disorders may present with chronic cough at this age including allergic rhinosinusitis, cystic fibrosis, pulmonary hemosiderosis, interstitial pneumonitis, and primary ciliary dyskinesia.

Mycoplasma pneumoniae infection is an important cause of chronic cough among school-age children. In its early stages, the disease is identical to a viral upper respiratory infection with coryza, sore throat, low-grade fever, and malaise. Gradually, the symptoms of lower respiratory involvement emerge and persist. Cough ranges from dry and hacking to one productive of mucoid sputum. On occasion the disease progresses to lobar pneumonia (Fig. 16-16, A and B) indistinguishable from typical bacterial pneumonia. The cough typically persists for 6 weeks, although it may last for 3 months. Physical findings tend to be minimal, although crackles and wheezing are often noted. The chest radiograph is not diagnostic, and the findings may be either interstitial or bronchopneumonic in character, with predilection for the lower lobes (see Fig. 16-16, A and B). Often the chest radiograph is normal. Diagnosis of M. pneumoniae infection can be made most rapidly by throat swab PCR. Serology is also used, and either paired sera for IgG titer or a single elevated IgM titer can be diagnostic. Mycoplasma culture is performed, but the organism is difficult and slow to isolate (taking 60 to 90 days), making this test of little clinical utility.

Figure 16-16 Pneumonia. A, Posteroanterior view and B, lateral view of Mycoplasma pneumonia in a 10-year-old boy. Posteroanterior chest radiograph shows right lower lobe (apical segment) involvement of a lobar infiltrative process.