Discussion:
With increasing use of bronchoscopic examination in paediatric patient and developing devices of suitable size for small children, airway malacia disorders are becoming well recognized. However, the true incidence of airway malacia is not well known. According to the English literature, two studies that enrolled the highest numbers of patients revealed that the incidence of airway malacia among patients underwent bronchoscopy is 16.6% and 34%. In the latter, authors included patients with laryngomalacia in their study 5,6. We found the incidence rate similar to the first study (16.6%). There are several reasons why the true incidence is not well known. There is no standardized diagnostic criterion of airway malacia. In 2019, ERS Task force report is suggested definition of airway malacia as greater the 50% expiratory reduction in the cross-sectional luminal area during quiet respiration; but some centres has used the 25% or 33% expiratory reduction for diagnosis 4. Furthermore, in some paediatric pulmonology centres, suitable bronchoscopy device for small infants or new-borns may not be available and lack of device may cause the diagnosis to be delayed or missed. Deficient knowledge or lack of suspicion of general practitioners, even of some paediatricians, about airway malacia may also cause the patients to be undiagnosed. A significant amount of patients with lower airway malacia might be misdiagnosed as asthma.
The type and onset of symptoms depend on localization and severity of the malacic segment. We did not evaluate the onset time in our study, but we found that the most common clinical symptom was recurrent and/or prolonged respiratory infection. The high percentages of respiratory infections in our study may be related to the higher number of cases with BM. Airway malacia is a frequent bronchoscopic finding in children with recurrent respiratory infection and protracted bacterial bronchitis, although it is not known exactly whether malacia is cause or result of respiratory infection 7,8. Only five of the BM cases with a history of recurrent and/or prolonged respiratory infection had positive BAL culture, and that represents 10.4% of all BM cases. Overall, 22.6% of BAL samples were culture positive. The cause of such a low rate may be related to take BAL samples while some of the patients were under antibiotic treatment.
The most common physical examination finding was stridor in our study. Stridor is mainly related to narrowing of extra thoracic airway. Although the most common airway malacia type was BM in our study, the high frequency of stridor might be related to accompanying laryngomalacia.
Airway malacias are classified as primary (congenital) and secondary (acquaried) malacia according to time of abnormal formation on the airways 4. Although no etiological factor could be found for eight patients to develope malacia in our study, it is difficult to classify them as primary airway malacia. Since, detecting persistence of a malacia during bronchoscopy despite proper treatment is necessary to name a malacia as primary. However, we did not perform any bronchoscopy after treatment to see whether malacia was persisting or not. Therefore, we did not make such a classification in our study.
In our study, the most common diseases associated with airway malacias were GERD and swallowing dysfunction. The relationship between GERD and airway malacia has been shown in several studies. The high prevalence of gastroesophageal reflux among infants with airways malacia can be related to the negative intrapleural pressure induced by airflow obstruction during respiration and this pressure leads to a malfunction of the lower gastroesophageal sphincter and causes reflux. It is also shown that after antireflux therapy; respiratory symptoms were decreased. The improvement may be related to preventing chronic injury to the lung or it may have occurred spontaneously.9,10. More detailed research is required to show this difference. Swallowing dysfunction is also common among airway malacias, or maybe we should say airway malacias are common in patients who have swallowing dysfunction. Although the reason of this association is not well known, it might be related to chronic inflammation of airways due to chronic aspiration.
There is no universally agreed gold standard diagnostic test for airway malacias; but flexible bronchoscopy is the most commonly used diagnostic modality. However, bronchoscopy is an invasive and subjective procedure. Furthermore, it increases end expiratory airway pressure and it can be difficult to detect some mild malacias during bronchoscopy. Chest CT is a valuable test to diagnose respiratory diseases. It could assist to find secondary factors causing malacia after diagnosis or show supporting findings such as stenosis, increased/decreased inflation. In recent years, contrast enhanced multi-detector computed tomography (MDCT) has become an alternative modality to aid in the diagnosis of airway malacia in children by obtaining information about the calibre change of the large airways at both end-inspiration and end-expiration (paired end-inspiratory and end-expiratory) 11. However, it is very difficult to apply this dynamic technique in paediatric patients, and it is available in limited numbers of tertiary centres. Although we diagnosed airway malacia by performing flexible bronchoscopy, 56 patients were also performed thoracic non-dynamic CT and 10 of them revealed narrowing of the airway on malacic region.
Previously airway malacia, especially congenital form, has been thought to be self-limited and improved by the second year of life without intervention 12. Although the majority of the patients were under two years old, none of them were followed without any intervention in our study.
Treatment of malacia depends on the aetiology and severity of the airway collapse. Treatment options include medical and surgical therapy, chest physiotherapy and ventilator support. However, there are no randomised-controlled studies for treatment in airway malacia.
One of the leading medical therapies in malacia is inhaled ipratropium bromide. Although its mechanism is not fully known, it is thought to have an effect on airway muscular tone. In recent animal and human studies showed airway dynamics of trachea are affected by tracheal smooth muscle contraction by cholinergic stimulation13,14. Although inhaled ipratropium bromide is an anticholinergic agent, it stimulates smooth muscle contraction by blocking presynaptic muscarinic receptors (M2), which provide feedback inhibition for acetylcholine release in the neuromuscular junction, in low doses 15. Relying on this effect, inhaled ipratropium bromide therapy was started in patients with malacia in our clinic. However, reliable data could not be obtained from our hospital records about the duration of inhaled ipratropium bromide therapy that improved the symptoms of the patients. In addition, none of the patients underwent control bronchoscopy to assess the improvement in the malacic region. There is only one study in the literature about the effect of 6 months of atropine treatment on clinical improvement; but no data were available when the treatment should be terminated 16.
Tracheostomy with or without long-term invasive MV was the mainstay of treatment for severe TM in the past. However, because of its life-threatening complications and remarkable advance in non-invasive therapies, tracheostomy without invasive MV is currently used as a last resort. In our study, tracheostomy was performed in 15% of the patients due to need for invasive MV however, invasive MV indication was not only airway malacia but also respiratory failure related to associated conditions in all of them. Non-invasive MV is another treatment method of malacia. Positive pressure creates a pneumatic stent and prevents the collapse of the airway during respiration 4. Although, only one patient, who had severe bronchomalacia on bilateral main bronchus, was treated with non-invasive MV in our study. we believe that, it will be the first treatment of choice for severe malacia in the future.