Tracheobronchomalacia in wheezing young children poorly responsive to asthma therapy
Authors: E. Baraldi, S. Donegà, S. Carraro, M. Farina, A. Barbato, C. Cutrone
Journal: Allergy (2009)

Recurrent wheezing is quite common in the early years of life and often prompts the prescription of long-term therapies with corticosteroids and bronchodilators, which in some cases are ineffective. The pathophysiology is still poorly understood and includes factors other than airway inflammation (1). Infants with persistent wheezing unresponsive to asthma treatment, who nonetheless thrive well and are well oxygenated are often call ‘Happy wheezers’, a term not seen in medical literature databases, but frequently used in clinical practice. Previous studies on children with recurrent wheezing who underwent flexible bronchoscopy (FB) demonstrated a marked prevalence of primary tracheobronchomalacia (TBM), which may mimic asthma, in the first years of life (2–5). The aim of this study was to report on the bronchoscopic findings in a group of children under 3 years of age referred to a tertiary center because of doctor-confirmed persistent/recurrent wheezing failing to respond to conventional asthma therapy. All cases of children under 3 years of age who underwent a clinically indicated FB (6) between January 2003 and December 2006 were drawn from our clinical database. Inclusion criteria were the following: referral for a diagnosis of persistent/recurrent wheezing poorly responsive to asthma therapies (i.e., trials of inhaled bronchodilators and corticosteroids and at least two courses of oral corticosteroids). Recurrent wheezing was defined as three or more episodes in the previous 6 months; persistent wheezing as symptoms occurring on most days of the week in the last 3 months and/or not disappearing completely between episodes. Exclusion criteria were the following: preterm birth, congenital heart disease, tracheo-esophageal fistula, and Down syndrome. FB was performed using a flexible bronchoscope (TypeBF3; Olympus, Japan), and images were videotaped (6). Children were sedated with i.v. propofol. Malacia was defined as a dynamic decrease in the diameter of the trachea with expiration >50% during quiet spontaneous breathing (5). Approval was obtained from the Padova Hospital Ethical Committee. Over the 4-year period, 130 children under 3 years of age underwent FB at our center as part of their diagnostic work-up. Thirty-three of these patients (mean age 12 months, range 4–36 m, 25 males) met the inclusion criteria. Twelve of these children (35%) were referred with a clinical diagnosis of ‘happy wheezers’. One child was atopic. Structural airway anomalies were found in 15 patients (44%). The final diagnosis was primary tracheo- or broncho-malacia in 14 patients (42%): five had tracheomalacia alone (Fig. 1), four bronchomalacia alone, and five had TBM. Tracheomalacia was localized in the middle third (60%) and lower third (40%) of the trachea. One patient had laryngomalacia unassociated with any TBM. It is worth noting that a bronchoscopic diagnosis of TBM was reached in 9/12 (75%) of the children diagnosed as ‘happy wheezers’. Bronchoscopic evidence of tracheomalacia with significant loss of airway caliber during expiration in a 16-month-old boy. Our study shows that recurrent/persistent wheezing failing to respond to conventional asthma therapy in children <3 years of age is often associated with TBM (42% of cases in our series), according with previous reports in children (2–5). The novelty of our study lies in that we investigated a subset of infants labeled as ‘happy wheezers’– and 75% of them revealed TBM at bronchoscopy. TBM is a weakness of the trachea and mainstem bronchi such that the airway is more susceptible to collapse during expiration (Fig. 1), causing airflow limitation and wheezing that may mimic asthma (5). Mild–moderate airway malacia is a self-limiting disease, and most infants grow out of the condition by the time they are 2–3 years old (4, 5). A recent report estimated the incidence of primary airway malacia to be at least 1/2100 children (4), supporting the conviction that TBM is underdiagnosed. In accordance with previous studies, we believe that FB is a safe and useful tool for achieving a definitive diagnosis and preventing any inappropriate asthma treatment (1, 4). Limits of our study are that the results cannot be generalized to all wheezing young children, because we studied a highly selected group, and that we cannot rule out the possibility of TBM and asthma coexisting in the same child. In conclusion, this study suggests that TBM is quite a common airway anomaly in children with recurrent/persistent wheezing failing to respond to conventional asthma therapy. We also suggest that many infants diagnosed as ‘happy wheezers’ may, in fact, have underlying tracheobronchomalacia.