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Clinical Investigations: Miscellaneous |

Tracheomalacia and Bronchomalacia in Children*: Incidence and Patient Characteristics FREE TO VIEW

Ruben Boogaard, MD; Sjoerd H. Huijsmans, MD; Marielle W. H. Pijnenburg, MD; Harm A. W. M. Tiddens, MD, PhD; Johan C. de Jongste, MD, PhD; Peter J. F. M. Merkus, MD, PhD
Author and Funding Information

*From Erasmus MC-Sophia Children’s Hospital, Erasmus University Medical Centre, Department of Pediatrics, Division of Pediatric Pulmonology, Rotterdam, the Netherlands.

Correspondence to: Ruben Boogaard, MD, Room Sb-2666, Sophia Children’s Hospital, Erasmus University Medical Centre Rotterdam, PO Box 2060, 3000 CB Rotterdam, the Netherlands; e-mail: r.boogaard@erasmusmc.nl



Chest. 2005;128(5):3391-3397. doi:10.1378/chest.128.5.3391
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Objective: Congenital airway malacia is one of the few causes of irreversible airways obstruction in children, but the incidence in the general population is unknown. Severe airway malacia or malacia associated with specific syndromes is usually recognized and diagnosed early in infancy, but information about clinical features of children with primary malacia, often diagnosed only later in childhood, is scarce.

Methods: We analyzed all flexible bronchoscopies performed between 1997 and 2004 in the Sophia Children’s Hospital, summarized clinical features of children with primary airway malacia, estimated the incidence of primary airway malacia, and calculated the predictive value of a clinical diagnosis of airway malacia by pediatric pulmonologists.

Results: In a total of 512 bronchoscopies, airway malacia was diagnosed in 160 children (94 males) at a median age of 4.0 years (range, 0 to 17 years). Airway malacia was classified as primary in 136 children and secondary in 24 children. The incidence of primary airway malacia was estimated to be at least 1 in 2,100. When pediatric pulmonologists expected to find airway malacia (based on symptoms, history, and lung function) prior to bronchoscopy, this was correct in 74% of the cases. In 52% of the airway malacia diagnoses, the diagnosis was not suspected prior to bronchoscopy. Presenting clinical features of children with airway malacia were variable and atypical, showing considerable overlap with features of allergic asthma. Peak expiratory flow was more reduced than FEV1.

Conclusion: Primary airway malacia is not rare in the general population, with an estimated incidence of at least 1 in 2,100 children. Airway malacia is difficult to recognize based on clinical features that show overlap with those of more common pulmonary diseases. We recommend bronchoscopy in patients with impaired exercise tolerance, recurrent lower airways infection, and therapy-resistant, irreversible, and/or atypical asthma to rule out airway malacia.

Figures in this Article

Congenital malacia of the large airways is one of the few causes of irreversible airways obstruction in children, with symptoms varying from recurrent wheeze and recurrent lower airways infections to severe dyspnea and respiratory insufficiency.14 Severe cases are usually detected in the neonatal period when children present with ventilator dependency or acute severe obstructive episodes with cyanosis. Airway malacia associated with specific syndromes or congenital heart disease may be detected in early life because of selective screening.3,56

Children with mild airway malacia often present after the neonatal period with nonspecific symptoms such as rattling, wheeze, stridor, exercise intolerance, cough, recurrent lower airway infections, and airways obstruction.3,7Because of the similarity in symptoms, the poor response to standard asthma treatment, and the irreversible nature of the airways obstruction, isolated airway malacia may be misdiagnosed for severe-persistent or therapy-resistant asthma.810

Consequently, if airway malacia remains undetected in childhood, patients may be treated unnecessarily with high doses of inhaled corticosteroids into adulthood for many years, and may be undertreated for recurrent lower airways infections, with the risk of additional damage to the lung and airways.

Based on percentages between 23% and 57% of observed airway malacia in pediatric bronchoscopic series, various authors1114 concluded that malacia of the central airways is more prevalent than previously thought, but general incidence data are lacking. This is partly due to the lack of an objective definition or classification of airway malacia3,7,12,15 and the lack of noninvasive diagnostic tests.

Previous series12,1617 about children with airway malacia focused mainly on the association with other conditions and on airway malacia diagnosed in young infants. However, less is known about clinical features in children with primary airway malacia diagnosed during childhood. We therefore focused on children who underwent bronchoscopy after referral to our outpatient clinic with persistent pulmonary symptoms, but who were otherwise healthy. The aims of this study were to estimate the incidence of primary airway malacia in the general population, to estimate the predictive value of a clinical diagnosis of airway malacia by pediatric pulmonologists, and to characterize the presenting symptoms and findings in patients diagnosed with primary airway malacia.

The study protocol fulfilled the ethical standards of the Dutch Pediatric Society. Because of the retrospective and noninterventional nature of our study, ethical approval and patient consent were judged unnecessary.

Study Subjects

In a descriptive, retrospective study the indication and outcome of all flexible bronchoscopies performed by pediatric pulmonologists in our hospital between 1997 and 2004 were evaluated. The Erasmus MC-Sophia Children’s Hospital is a tertiary referral center for the southwest of the Netherlands with an adherence population of 4.4 million. Flexible pediatric bronchoscopies within this region are only carried out in this referral hospital.

Definitions

Primary airway malacia was defined as airway malacia in otherwise normal infants.7 Secondary airway malacia was defined as airway malacia secondary to esophageal atresia, VATER/VACTERL association (condition with vertebral anomalies, anal atresia, congenital heart disease, tracheoesophageal fistula or esophageal atresia, renourinary anomalies, or radial limb defects), vascular or other external compression of the airways, or specific syndromes.

Incidence and Clinical Features

The incidence of primary airway malacia was calculated assuming that malacia is congenitally present and not acquired, and that the annual detection rate of isolated airway malacia was fairly constant and thus reflecting the annual incidence in the population. In outpatients who underwent bronchoscopy because of diagnostic or therapeutic workup, we calculated the predictive value of a clinical diagnosis of airway malacia made by pediatric pulmonologists prior to bronchoscopy. In otherwise healthy patients with a diagnosis of primary airway malacia, we conducted a detailed review of the clinical features, including presenting symptoms and signs, lung function data, bacterial cultures and the lipid-laden macrophage index (LLMI)—scored according to Corwin and Irwin18—from the BAL fluid. Clinical features of patients with a concurrent medical condition such as cystic fibrosis (CF) or an immunologic disorder were not analyzed because we wanted to be informed about symptoms that could be attributed to the airway malacia.

Data from in-hospital bronchoscopies were excluded from these analyses, because we wanted to gain insight in the clinical features of patients who underwent bronchoscopy during a diagnostic workup at the outpatient clinic; in-hospital bronchoscopies are often performed in children with different pathologic conditions.

Bronchoscopic Examination

Bronchoscopies were carried out by a pediatric pulmonologist as part of diagnostic workup in routine patient care, using a flexible bronchoscope with external diameter 3.5 mm or 5.5 mm (Olympus; Tokyo, Japan) during general anesthesia. Airway malacia was diagnosed by visual inspection of airway shape and dynamics during spontaneous breathing without positive end-expiratory pressure, or during coughing. Malacia was defined as collapse of at least 50% of the airway lumen, during expiration, cough or spontaneous breathing, or a ratio of cartilage to membranous wall area of < 3:1.7 Bronchoscopies were recorded on videotape and reevaluated by at least one independent experienced pediatric pulmonologist. Only when consensus between observers existed on the diagnosis airway malacia, children were labeled as such. BAL was carried out according to recommendations,19 when lower airway infection and/or aspiration were expected on clinical grounds. Antibiotic treatment was discontinued 48 h in advance of bronchoscopy.

Statistics

All data are summarized using descriptive statistics.

Between 1997 and 2004, a total of 512 bronchoscopies were performed (Fig 1 ). In 324 children (193 male) with a median (range) age of 4.4 (0 to 18) years referred to our outpatient clinic, bronchoscopy was performed as part of a diagnostic workup. In 188 children, bronchoscopy was performed during a hospital admission. The indications for bronchoscopy are summarized in Table 1 .

Primary airway malacia was diagnosed in 136 children (80 male) with a median (range) age of 4.3 (0 to 17) years (male/female ratio, 1.4:1). Tracheomalacia was present in 63 children (46%), tracheobronchomalacia in 49 children (36%), and bronchomalacia in 24 children (18%). The bronchomalacia was located on the left in 33 children, on the right in 21 children, and on both sides in 19 children. Secondary airway malacia was found in 24 children; airway malacia was secondary to esophageal atresia or VACTERL association (n = 11), a congenital heart defect with compression of the bronchial tree (n = 9), a vascular ring (n = 2). or a bronchogenic cyst with compression (n = 2).

Incidence Estimate

Based on the annual birth rate of 50,000 in the region of adherence, assuming primary airway malacia as congenital, and a constant detection rate of 17 cases per year (136 cases in 7 years), it was estimated that the incidence of primary airway malacia was about 1 in every 2,600 newborns. An incidence estimate based on bronchoscopic findings from the last 4 years of the survey (from 2001 to 2004) was 1 in 2,100 children (95 cases in 4 years).

Predictive Value of a Clinically Expected Diagnosis of Airway Malacia Prior to Bronchoscopy

In the 324 out-of-clinic patients, airway malacia was found in 126 patients (115 cases of primary airway malacia). Prior to bronchoscopy, pediatric pulmonologists expected a malacia, based on history, physical examination, and/or lung function in 82 patients of whom 61 actually had malacia (positive predictive value, 74%). In 65 of 126 patients, airway malacia was not suspected prior to bronchoscopy (false-negative rate of 52%).

Primary Airway Malacia: Clinical Features

From the 115 patients with primary airway malacia diagnosed at the outpatient clinic, 96 patients (58 male) with a median age of 5.2 years (range, 0 to 16 years) had no concurrent medical conditions (isolated malacia). The presenting symptoms of those children are stated in Table 2 . Nineteen patients with primary airway malacia also had a concurrent medical condition (eg, CF, immunodeficiency, Down syndrome), probably influencing their presenting clinical features, and were therefore not analyzed.

At time of referral to our outpatient clinic, 70 of 96 patients (73%) with primary airway malacia were using asthma medication. The pediatric pulmonologist diagnosed asthma or probable asthma in 30 patients (31%) with airway malacia.

Lung function was performed by 45 children (Table 3 ). Mean peak expiratory flow (PEF), FEV1, and FEV1/FVC were below predicted values. In most patients, lung function values did not improve with bronchodilatation. A typical flow-volume curve of a child with tracheomalacia is presented in Figure 2 .

In 86 of 96 children with an airway malacia without a concurrent medical condition, BAL fluid was obtained. In 67 children, at least one pathogen was cultured. Haemophilus influenza B, Streptococcus pneumoniae, and Staphylococcus aureus were cultured in 34%, 30%, and 22% of the BALs, respectively. In 75 children, LLMI was determined in the BAL fluid. Median LLMI was 18 (range, 0 to 253). The LLMI did not correlate with age. In 14 children (20%), the LLMI was increased and thus indicative of aspiration.18

Based on retrospective bronchoscopic data from a 7-year period, we estimated the incidence of primary airway malacia in the general population, assessed the positive predictive value of a clinical diagnosis of malacia prior to bronchoscopy by pediatric pulmonologists, and evaluated the clinical features of children with primary airway malacia. Primary airway malacia was diagnosed in 136 patients in 7 years, implying an incidence of at least 1 in 2,600 newborns. When analyzing bronchoscopies from the last 4 years of the survey, the estimated incidence of primary airway malacia was even higher: 1 in 2,100 newborns. This increased incidence estimate probably does not reflect a true rise in incidence, but may reflect a greater awareness of airway malacia by pediatric pulmonologists, and a lower threshold to perform bronchoscopy in children with atypical respiratory problems. Moreover, our incidence estimate is a conservative one because of selection bias. Bronchoscopy was only conducted in referred patients, and it is likely that many patients with airway malacia and minor symptoms were not referred.

Other series1,1114 also suggest that airway malacia is a relatively common disorder, but incidence estimates are not provided and differences in patient selection make it difficult to compare with these series. Moreover, a uniformly accepted definition of airway malacia is lacking and the bronchoscopic diagnosis of airway malacia is based on subjective evaluation by the bronchoscopist, making comparisons between studies difficult.

When pediatric pulmonologists expected to find a malacia prior to bronchoscopy, this was correct in three fourths of the patients. However, in one half of the patients with airway malacia, the diagnosis was not suspected prior to bronchoscopy. Hence, experienced specialized clinicians have difficulty in recognizing primary airway malacia based on clinical features. Furthermore, the most frequent presenting symptoms were cough, dyspnea, recurrent lower airways infection, recurrent rattling and wheeze, and reduced exercise tolerance, showing considerable overlap with features of asthma and chronic bronchitis. These factors imply that children with isolated airway malacia are easily misdiagnosed and treated for the wrong disease, such as asthma. This is supported by the fact that a large majority of the patients with airway malacia were using asthma medication at time of referral, while a pediatric pulmonologist diagnosed asthma in only 40% of these children. A typical, barking, or seal-like cough is often described as an indicative symptom in airway malacia2,4,16 but was only mentioned in less than one half of the patients with isolated airway malacia.

In the majority of patients, we obtained positive bacterial culture findings in the BAL fluid, consistent with the clinical impression of chronic bacterial bronchitis secondary to the expected impaired mucociliary clearance in children with airway malacia.2,13

The LLMI was routinely assessed in the BAL fluid as an additional step in the diagnostic workup for aspirations. The large majority of the patients with isolated airway malacia had no evidence of aspirations based on the LLMI. These data are not consistent with reports3,11,20 that suggest that aspiration is a frequent complication of airway malacia. The older age at diagnosis and the exclusion of patients with associated syndromes and medical conditions (who are at greater risk of aspiration) in our series may explain this difference.

Lung function measurements in patients with isolated airway malacia demonstrated airways obstruction not improving after bronchodilatation, with a considerable reduction of PEF, being much more affected than FEV1. The reduced PEF and FEV1 are compatible with the increased central airway collapsibility during forced expiration.

The limitation of this study is the retrospective nature of the survey that could have affected the accuracy of the data collection of clinical features from the medical records. However, at our department a standardized medical record is kept, in which presenting signs and symptoms are collected uniformly. Comparisons with other retrospective studies on airway malacia may be difficult because of differences in population and diagnostic protocols, definition of airway malacia, and application and availability of flexible bronchoscopy.

Tracheomalacia and bronchomalacia were the topic of an excellent and thorough recent review in CHEST.1 The present study provides some additional data and aspects of this disorder that are clinically relevant. According to the review article,1 mild-to-moderate airway malacia is a self-limiting disease and most infants outgrow the condition by the age of 2 years. In addition, it was stated that the delay from the onset of symptoms to diagnosis was not > 144 weeks.1 Our study demonstrates that a substantial number of cases are diagnosed much later in childhood. Possibly, this difference between the studies is explained by differences in clinical severity of malacia. Nevertheless, our study suggests that there are a considerable number of children with airway malacia, in whom the diagnosis is made relatively late in life or not at all, and that airway malacia can be very difficult to recognize.

High-speed multidetector CT and specialized imaging provide novel diagnostic possibilities to diagnose airway malacia noninvasively.21 This provides a diagnostic opportunity for children in whom invasive bronchoscopy cannot be performed. Nevertheless, in the majority of young children, bronchoscopy will be mandatory to diagnose airway malacia, because it is difficult to image the airway during dynamic maneuvers in young children due to their inability to perform breathing instructions.

What is the clinical relevance of this study? It suggests that the incidence of primary airway malacia is at least 1 in 2,100. Furthermore, it seems likely that a considerable proportion of pediatric (and probably adult) patients with atypical or recurrent respiratory symptoms, irreversible chronic airways obstruction labeled COPD or asthma,10,22or with persistent troublesome cough2324 do not have isolated airway malacia diagnosed. A correct diagnosis of airway malacia is important for several reasons: (1) the therapeutic approach is fundamentally different, being focused on treatment or prevention of lower airways infections and improvement of mucociliary clearance, sometimes even including surgery23,2526; (2) the patient and his/her family benefit from a sound explanation for the exercise intolerance (caused by the dynamic airway collapse) that may be present lifelong; (3) for both pediatrician and chest physician, the irreversibility of airways obstruction is sufficiently explained and will lead to less prescription of asthma drugs that are not necessary in most cases and may have side effects. Children with both asthma and airway malacia pose a therapeutic challenge. Lung deposition of inhaled corticosteroids may be negatively affected by severe airways obstruction and anatomic abnormalities, resulting in less efficacy of asthma treatment and worse long-term outcome, as was found in asthmatic patients who start off with lower lung function in childhood.22

We conclude that primary airway malacia is a common disorder in the general population. Many of our patients had bacterial lower airways infections but no indications of aspirations based on the bronchoscopic findings. The most striking lung function abnormality in our population was a decreased PEF, which appeared more affected than FEV1.

Presenting symptoms of isolated airway malacia are atypical and also for pediatric pulmonologists difficult to recognize. As a correct diagnosis is important because of the therapeutic implications and perhaps lifelong consequences, we recommend considering bronchoscopy in all patients with unexplained exercise intolerance, recurrent lower airways infection, and irreversible and/or atypical asthma.

Abbreviations: CF = cystic fibrosis; LLMI = lipid-laden macrophage index; PEF = peak expiratory flow

This study was performed in the Sophia Children’s Hospital, Rotterdam.

Table Graphic Jump Location
Table 1. Indications for Bronchoscopy*
* 

For each bronchoscopy, one to three indications could be noted. Results are presented as No. (%) unless otherwise indicated.

Table Graphic Jump Location
Table 2. Clinical Features in 96 Outpatients With Primary Airway Malacia and Without a Concurrent Medical Condition
Table Graphic Jump Location
Table 3. Lung Function Data (Percentage of Predicted) From Outpatients With Primary Airway Malacia and Without a Concurrent Medical Condition*
* 

Data are presented as mean (SD). MEF25 = mean expiratory flow at 25% of vital capacity remaining in the lung.

Figure Jump LinkFigure 2. A typical flow-volume curve of a child with tracheomalacia: a decreased PEF, with slight deterioration after bronchodilatation.Grahic Jump Location
Carden, KA, Boiselle, PM, Waltz, DA, et al (2005) Tracheomalacia and tracheobronchomalacia in children and adults: an in-depth review.Chest127,984-1005. [CrossRef] [PubMed]
 
Clements, B Congenital malformations of the lungs and airways. Taussig, LM Landau, LI eds.Pediatric respiratory medicine1999,1106-1136 Mosby. St. Louis, MO:
 
Austin, J, Ali, T Tracheomalacia and bronchomalacia in children: pathophysiology, assessment, treatment and anaesthesia management.Paediatr Anaesth2003;13,3-11. [CrossRef] [PubMed]
 
McNamara, VM, Crabbe, DC Tracheomalacia.Paediatr Respir Rev2004;5,147-154. [CrossRef] [PubMed]
 
Lee, SL, Cheung, YF, Leung, MP, et al Airway obstruction in children with congenital heart disease: assessment by flexible bronchoscopy.Pediatr Pulmonol2002;34,304-311. [CrossRef] [PubMed]
 
Rock, MJ, Green, CG, Pauli, RM, et al Tracheomalacia and bronchomalacia associated with Larsen syndrome.Pediatr Pulmonol1988;5,55-59. [CrossRef] [PubMed]
 
Benjamin, B Tracheomalacia in infants and children.Ann Otol Rhinol Laryngol1984;93,438-442. [PubMed]
 
Cohn, JR Localized bronchomalacia presenting as worsening asthma.Ann Allergy1985;54,222-223. [PubMed]
 
Chung, KF, Godard, P, Adelroth, E, et al Difficult/therapy-resistant asthma: the need for an integrated approach to define clinical phenotypes, evaluate risk factors, understand pathophysiology and find novel therapies. ERS Task Force on Difficult/Therapy-Resistant Asthma.Eur Respir J1999;13,1198-1208. [PubMed]
 
Lavins, BJ, Hamilos, DL Distal airway bronchomalacia resulting in severe obstructive airway physiology.Chest1990;97,489-491. [CrossRef] [PubMed]
 
Schellhase, DE, Fawcett, DD, Schutze, GE, et al Clinical utility of flexible bronchoscopy and bronchoalveolar lavage in young children with recurrent wheezing.J Pediatr1998;132,312-318. [CrossRef] [PubMed]
 
Masters, IB, Chang, AB, Patterson, L, et al Series of laryngomalacia, tracheomalacia, and bronchomalacia disorders and their associations with other conditions in children.Pediatr Pulmonol2002;34,189-195. [CrossRef] [PubMed]
 
Chang, AB, Boyce, NC, Masters, IB, et al Bronchoscopic findings in children with non-cystic fibrosis chronic suppurative lung disease.Thorax2002;57,935-938. [CrossRef] [PubMed]
 
Finder, JD Primary bronchomalacia in infants and children.J Pediatr1997;130,59-66. [CrossRef] [PubMed]
 
Nicolai, T Pediatric bronchoscopy.Pediatr Pulmonol2001;31,150-164. [CrossRef] [PubMed]
 
Mair, EA, Parsons, DS Pediatric tracheobronchomalacia and major airway collapse.Ann Otol Rhinol Laryngol1992;101,300-309. [PubMed]
 
Sanchez, I, Navarro, H, Mendez, M, et al Clinical characteristics of children with tracheobronchial anomalies.Pediatr Pulmonol2003;35,288-291. [CrossRef] [PubMed]
 
Corwin, RW, Irwin, RS The lipid-laden alveolar macrophage as a marker of aspiration in parenchymal lung disease.Am Rev Respir Dis1985;132,576-581. [PubMed]
 
de Blic, J, Midulla, F, Barbato, A, et al Bronchoalveolar lavage in children. ERS Task Force on bronchoalveolar lavage in children.Eur Respir J2000;15,217-231. [CrossRef] [PubMed]
 
Bibi, H, Khvolis, E, Shoseyov, D, et al The prevalence of gastroesophageal reflux in children with tracheomalacia and laryngomalacia.Chest2001;119,409-413. [CrossRef] [PubMed]
 
Boiselle, PM, Ernst, A Recent advances in central airway imaging.Chest2002;121,1651-1660. [CrossRef] [PubMed]
 
Rasmussen, F, Taylor, DR, Flannery, EM, et al Risk factors for airway remodeling in asthma manifested by a low postbronchodilator FEV1/vital capacity ratio: a longitudinal population study from childhood to adulthood.Am J Respir Crit Care Med2002;165,1480-1488. [CrossRef] [PubMed]
 
Wood, RE Localized tracheomalacia or bronchomalacia in children with intractable cough.J Pediatr1990;116,404-406. [CrossRef] [PubMed]
 
Irwin, RS, Madison, JM The persistently troublesome cough.Am J Respir Crit Care Med2002;165,1469-1474. [CrossRef] [PubMed]
 
Kamata, S, Usui, N, Sawai, T, et al Pexis of the great vessels for patients with tracheobronchomalacia in infancy.J Pediatr Surg2000;35,454-457. [CrossRef] [PubMed]
 
Malone, PS, Kiely, EM Role of aortopexy in the management of primary tracheomalacia and tracheobronchomalacia.Arch Dis Child1990;65,438-440. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 2. A typical flow-volume curve of a child with tracheomalacia: a decreased PEF, with slight deterioration after bronchodilatation.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Indications for Bronchoscopy*
* 

For each bronchoscopy, one to three indications could be noted. Results are presented as No. (%) unless otherwise indicated.

Table Graphic Jump Location
Table 2. Clinical Features in 96 Outpatients With Primary Airway Malacia and Without a Concurrent Medical Condition
Table Graphic Jump Location
Table 3. Lung Function Data (Percentage of Predicted) From Outpatients With Primary Airway Malacia and Without a Concurrent Medical Condition*
* 

Data are presented as mean (SD). MEF25 = mean expiratory flow at 25% of vital capacity remaining in the lung.

References

Carden, KA, Boiselle, PM, Waltz, DA, et al (2005) Tracheomalacia and tracheobronchomalacia in children and adults: an in-depth review.Chest127,984-1005. [CrossRef] [PubMed]
 
Clements, B Congenital malformations of the lungs and airways. Taussig, LM Landau, LI eds.Pediatric respiratory medicine1999,1106-1136 Mosby. St. Louis, MO:
 
Austin, J, Ali, T Tracheomalacia and bronchomalacia in children: pathophysiology, assessment, treatment and anaesthesia management.Paediatr Anaesth2003;13,3-11. [CrossRef] [PubMed]
 
McNamara, VM, Crabbe, DC Tracheomalacia.Paediatr Respir Rev2004;5,147-154. [CrossRef] [PubMed]
 
Lee, SL, Cheung, YF, Leung, MP, et al Airway obstruction in children with congenital heart disease: assessment by flexible bronchoscopy.Pediatr Pulmonol2002;34,304-311. [CrossRef] [PubMed]
 
Rock, MJ, Green, CG, Pauli, RM, et al Tracheomalacia and bronchomalacia associated with Larsen syndrome.Pediatr Pulmonol1988;5,55-59. [CrossRef] [PubMed]
 
Benjamin, B Tracheomalacia in infants and children.Ann Otol Rhinol Laryngol1984;93,438-442. [PubMed]
 
Cohn, JR Localized bronchomalacia presenting as worsening asthma.Ann Allergy1985;54,222-223. [PubMed]
 
Chung, KF, Godard, P, Adelroth, E, et al Difficult/therapy-resistant asthma: the need for an integrated approach to define clinical phenotypes, evaluate risk factors, understand pathophysiology and find novel therapies. ERS Task Force on Difficult/Therapy-Resistant Asthma.Eur Respir J1999;13,1198-1208. [PubMed]
 
Lavins, BJ, Hamilos, DL Distal airway bronchomalacia resulting in severe obstructive airway physiology.Chest1990;97,489-491. [CrossRef] [PubMed]
 
Schellhase, DE, Fawcett, DD, Schutze, GE, et al Clinical utility of flexible bronchoscopy and bronchoalveolar lavage in young children with recurrent wheezing.J Pediatr1998;132,312-318. [CrossRef] [PubMed]
 
Masters, IB, Chang, AB, Patterson, L, et al Series of laryngomalacia, tracheomalacia, and bronchomalacia disorders and their associations with other conditions in children.Pediatr Pulmonol2002;34,189-195. [CrossRef] [PubMed]
 
Chang, AB, Boyce, NC, Masters, IB, et al Bronchoscopic findings in children with non-cystic fibrosis chronic suppurative lung disease.Thorax2002;57,935-938. [CrossRef] [PubMed]
 
Finder, JD Primary bronchomalacia in infants and children.J Pediatr1997;130,59-66. [CrossRef] [PubMed]
 
Nicolai, T Pediatric bronchoscopy.Pediatr Pulmonol2001;31,150-164. [CrossRef] [PubMed]
 
Mair, EA, Parsons, DS Pediatric tracheobronchomalacia and major airway collapse.Ann Otol Rhinol Laryngol1992;101,300-309. [PubMed]
 
Sanchez, I, Navarro, H, Mendez, M, et al Clinical characteristics of children with tracheobronchial anomalies.Pediatr Pulmonol2003;35,288-291. [CrossRef] [PubMed]
 
Corwin, RW, Irwin, RS The lipid-laden alveolar macrophage as a marker of aspiration in parenchymal lung disease.Am Rev Respir Dis1985;132,576-581. [PubMed]
 
de Blic, J, Midulla, F, Barbato, A, et al Bronchoalveolar lavage in children. ERS Task Force on bronchoalveolar lavage in children.Eur Respir J2000;15,217-231. [CrossRef] [PubMed]
 
Bibi, H, Khvolis, E, Shoseyov, D, et al The prevalence of gastroesophageal reflux in children with tracheomalacia and laryngomalacia.Chest2001;119,409-413. [CrossRef] [PubMed]
 
Boiselle, PM, Ernst, A Recent advances in central airway imaging.Chest2002;121,1651-1660. [CrossRef] [PubMed]
 
Rasmussen, F, Taylor, DR, Flannery, EM, et al Risk factors for airway remodeling in asthma manifested by a low postbronchodilator FEV1/vital capacity ratio: a longitudinal population study from childhood to adulthood.Am J Respir Crit Care Med2002;165,1480-1488. [CrossRef] [PubMed]
 
Wood, RE Localized tracheomalacia or bronchomalacia in children with intractable cough.J Pediatr1990;116,404-406. [CrossRef] [PubMed]
 
Irwin, RS, Madison, JM The persistently troublesome cough.Am J Respir Crit Care Med2002;165,1469-1474. [CrossRef] [PubMed]
 
Kamata, S, Usui, N, Sawai, T, et al Pexis of the great vessels for patients with tracheobronchomalacia in infancy.J Pediatr Surg2000;35,454-457. [CrossRef] [PubMed]
 
Malone, PS, Kiely, EM Role of aortopexy in the management of primary tracheomalacia and tracheobronchomalacia.Arch Dis Child1990;65,438-440. [CrossRef] [PubMed]
 
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