Case 1: A long history of cough and dyspnea

A 10-year-old girl presented with a nine-year history of six to eight upper and lower respiratory tract infections annually, each with a duration of three to six weeks in spite of antibiotic treatment, accompanied with cough, dyspnea and occasional wheezing. She also reported these symptoms during physical exercise, independent of infections. Until now, three pneumonias and multiple bronchitic episodes had been verified. At five years of age, she was diagnosed with bronchial asthma. For two years, treatment consisted of intermittent courses of short-acting beta-agonists and inhaled corticosteroids, before she was switched to a daily combination treatment with long-acting beta-agonists and inhaled corticosteroids (budesonide-formoterol 160 μg/4.5 μg twice daily) plus montelukast 5 mg orally without any breakthrough. A sweat test performed at four years of age was normal, as was a skin prick test to common aeroallergens and measurements of exhaled nitric oxide. Previous lung function tests were reported as a bronchial obstruction with no or only partial bronchodilator response. On presentation, the child was afebrile with normal vital signs, including an oxygen saturation of 97% on room air. A physical examination was unremarkable except for a prolonged expiration on auscultation. A complete blood count was normal and the erythrocyte sedimentation rate was 18 mm/h (0 mm/h to 10 mm/h). Further workup revealed the diagnosis.

CASE 1 DIAGNOSIS: DISTAL TRACHEOMALACIA AND STENOSIS AT THE ORIGIN OF THE RIGHT MIDDLE LOBE BRONCHUS

While the chest x-ray and another sweat test were unremarkable, spirometry showed a mid-expiratory flow limitation on the flow-volume loops, unresponsive to bronchodilator challenge (Figure 1). This is suggestive of an intrathoracic airway stenosis. Exercise-induced bronchoconstriction could not be demonstrated (standardized 8 min exercise challenge using a treadmill). These results were suggestive of a partial central airway obstruction. Flexible bronchoscopy under general anesthesia with spontaneous ventilation confirmed a distal tracheomalacia with partial narrowing of the airway lumen due to a prolapse of the membranous trachea (Figure 2), and revealed a stenosis of the right middle lobe bronchus at its origin. The asthma medications were discontinued, and the girl and her family were taught home chest physiotherapy exercises including the use of portable positive expiratory pressure and flutter devices for the event of lower respiratory infections. Follow-up visits after more than one year were unremarkable except for two short-lived upper respiratory tract infections. The girl became physically active and her quality of life improved dramatically.

Figure 1).

Spirometry shows a nonreversible mid-expiratory flow limitation

Figure 2).

Flexible bronchoscopy shows a reduced anterior-posterior diameter of distal trachea due to a prolapse of the distal part of the membranous trachea during expiration

Tracheomalacia results from missing, hypoplastic or unusually soft tracheal cartilage. In the majority of cases, such as in the present case, the intrathoracic part and especially the lower one-third of the trachea is affected. The reduced cartilage support may lead to variable extensive collapse of the affected part of the trachea, notably when the intrathoracic pressure exceeds the intratracheal pressure as with forced expiration, eg, due to coughing or crying. Tracheomalacia may be primary (congenital) or secondary due to an external compression (eg, from vascular abnormalities such as a vascular ring due to a double aortic arch or an aberrant innominate artery), can be acquired (eg, as a consequence of long-term mechanical ventilation), or may be associated with a tracheo-esophageal fistula or a connective tissue disorder. While long-lasting external compression (such as from vascular abnormalities) locally disturbs the development of the tracheal cartilage, tracheomalacia secondary to long-term intubation or tracheostomy with or without mechanical ventilation is most likely due to a chronic perichondritis resulting from pressure and local inflammatory processes (1).

Clinical symptoms include stridor, barking cough, wheezing, dyspnea, feeding problems, and recurrent and prolonged respiratory infections. Therefore, as in our case, the condition might be mistaken for other disorders, such as bronchial asthma (2). Tracheomalacia is predominantly symptomatic in infants and is one of the main causes of stridor in this age group. It is usually benign and self-limiting, with major improvement or resolution of symptoms within the first year of life, chiefly because of an increase in smooth muscle tone and rigidity of the cartilage. In more severe cases, tracheomalacia may be associated with significant morbidity and mortality. In all children with evidence of airway obstruction unresponsive to bronchodilators, the differential diagnoses need to be carefully explored.

Although invasive, flexible bronchoscopy with maintained spontaneous ventilation is considered the investigation of choice. On chest x-ray, an invisible carina or distal trachea can be suggestive. Fluoroscopy and computed tomography (CT) scanning can also be diagnostic, but require exposure to radiation. However, if a secondary tracheomalacia from an external compression is suspected, further imaging with CT or magnetic resonance imaging is needed. In older children, a spirometry with flow-volume loops is useful and, as in the present patient with intrathoracic tracheomalacia, typically shows an expiratory flow limitation with a flow plateau.

Because tracheomalacia in the majority of cases is self-limited, a conservative approach should be attempted if clinically possible. In severe cases, continuous positive airway pressure, or if not sufficient or not feasible, surgical procedures such as aortopexy might be needed. Tracheostomy and long-term mechanical ventilation have been more readily used in the past, but are nowadays, due to the various associated problems, reserved for otherwise unmanageable cases. Beta₂-agonists should be used very cautiously in affected infants, because they could potentially worsen symptoms by reducing smooth muscle tone and thus increasing tracheal collapsibility (3).

CLINICAL PEARLS

• Tracheomalacia, even though a rare cause for persistent cough, wheezing and dyspnea on exertion, should be considered in all patients with asthma-like symptoms and bronchial obstruction without proper response to beta-agonists and inhaled steroids, especially when accompanied by frequent and prolonged respiratory tract infections. Other differential diagnoses to consider include, among others, gastroesophageal reflux, infections such as pertussis and Mycoplasma pneumoniae, cystic fibrosis, primary ciliary dyskinesia, immunodeficiencies, vocal cord dysfunction and habitual cough.

• While spirometry can be suggestive, a flexible bronchoscopy is indicated to confirm the diagnosis. Imaging studies, such as CT scans or magnetic resonance imaging, are required when a secondary tracheomalacia from external compression is suspected.

• Because the majority of cases are self-limited, a conservative approach should be attempted if clinically possible. For severe cases, other therapeutical options include continuous positive airway pressure, aortopexy, or, rarely, tracheal stents or tracheostomy. Beta₂-agonists in infants should be used with caution because they could potentially aggravate symptoms.