Congenital Airway Research Articles

Bronchoscopic findings of the suspected congenital upper airway anomalies

Bronchoscopic findings of the suspected congenital upper airway anomalies

Result of airway reconstruction by slide tracheobronchoplasty in children with congenital heart diseases and severe airway stenosis at Hanoi Heart Hospital: A series case report

Abstract: Congenital airway stenosis (tracheobronchial stenosis) in children is rare, difficult to treat and become more complex when associated with congenital heart defects. In severe airway stenosis, slide tracheobronchoplasty is the most optimal strategy to manage this condition, yet really challenging. We report case series with this combined condition of airway stenosis and congenital heart diseases, which were successfully treated by slide tracheobronchoplasty with concomitant heart repair. We also discuss about the indication, surgical technique as well as postoperative care.

Asthma as a Developmental Disorder

Asthma is the most common disorder in childhood, affecting six million children in the United States. Asthma is a heterogeneous disease, but most cases either start in early life or have their roots in events occurring in utero or during the preschool years. Protective or harmful exposures, including to environmental microbes, occurring during critical developmental windows determine patterns of immune responses that often persist for a lifetime. Air pollution, tobacco smoke, and prematurity can cause congenital airway narrowing, and newborns with decreased airway function are at risk for having asthma symptoms up to adulthood. Effects of environmental exposures are modified by common genetic variations and may also be mediated by prenatal changes in the epigenetic structure of the genome. Based on this evidence, we have postulated that asthma should be considered a developmental disorder, and this concept may be applicable to other chronic medical conditions affecting both children and adults.

Three-Dimensional Analysis of Human Laryngeal and Tracheobronchial Cartilages during the Late Embryonic and Early Fetal Period

Laryngeal and tracheobronchial cartilages are present as unique U-shaped forms around the respiratory tract and contribute to the formation of rigid structures required for the airway. Certain discrepancies still exist concerning cartilage formation in humans. To visualize the accurate timeline of cartilage formation, tracheobronchial and laryngeal cartilages were 3D reconstructed based on serial tissue sections during the embryonic period (Carnegie stage [CS] 18–23) and early fetal period (crown rump length [CRL] = 35–45 mm). The developmental phases of the cartilage were estimated by histological studies, which were performed on the reconstructed tissue sections. The hyoid greater horns were recognizable at CS18 (phase 2). Fusion of 2 chondrification centers in the mid-sagittal region was observed at CS19 in the hyoid bone, at CS20 in the cricoid cartilage, and in the specimen with CRL 39 mm in the thyroid cartilage. Phase 3 differentiation was observed at the median part of the hyoid body at CS19, which was the earliest among all other laryngeal and tracheobronchial cartilages. Most of the laryngeal cartilages were in phase 3 differentiation at CS22 and in phase 4 differentiation at CS23. The U-shaped tracheobronchial cartilages with phase 2 differentiation covered the entire extrapulmonary region at CS20. Phase 3 differentiation started on the median section and propagates laterally at CS21. The tracheobronchial cartilages may form simultaneously during the embryonic period at CS22-23 and early fetal periods, similar to adults in number and distribution. The spatial propagation of the tracheal cartilage differentiation provided in the present study indicates that cartilage differentiation may have propagated differently on phase 2 and phase 3. This study demonstrates a comprehensible timeline of cartilage formation. Such detailed information of the timeline of cartilage formation would be useful to improve our understanding of the development and pathophysiology of congenital airway anomalies.

Validity of flexible bronchoscopy in the diagnosis of chronic cough in children attending Assiut university children hospital

Context Chronic cough in children is a major health problem with an increased prevalence from 8 to 20.78% between 1999 and 2016. Flexible bronchoscope has become one of the most valuable tools in the diagnostic workup of unexplained chronic cough in children. Aims To assess the children with chronic cough using flexible bronchoscopy in order to diagnose the underlying causes that remain otherwise unexplained by noninvasive diagnostic tests. Settings and design Observational cohort study. Patients and methods Children with unexplained chronic cough underwent flexible bronchoscopy during the period from October 2017 to December 2019. Bronchoalveolar lavage (BAL) was done for cytologic examination and microbiologic studies. Results This study involved 60 children, aged from 2 months to 14 years. Flexible bronchoscopy demonstrated positive findings in 65% of cases. The most common finding was congenital airway anomalies in 25% of cases. The second most common finding was visible bronchitis in 21.67% of cases. Other bronchoscopic findings included endobronchial mucous plug (5%), foreign body aspiration (6.67%), extrinsic compression on the airways (10%), and adenoid hypertrophy (1.66%). Cytologic examination of BAL fluid showed that neutrophilia was the most common finding. Haemophilus influenzae was the most common isolated organism in the BAL fluid samples. Conclusions Flexible bronchoscopy is a valuable safe tool in the diagnosis of chronic cough in children. BAL helped in the diagnosis of the underlying etiology by providing samples for cytologic and microbiologic studies.

Congenital airway anomalies

Congenital airway anomalies (CAA) include a variety of conditions that cause respiratory distress in neonates and infants. These malformations occur at various anatomic levels and manifest in a wide spectrum of airway symptoms, with presentation significantly influenced by the level at which obstruction occurs as well as by the severity of obstruction. The prevalence of congenital airway malformations has been estimated to range between 0.2 and 1 in 10,000 live births. The most frequent CAA are laryngomalacia, bilateral vocal cord paralysis, subglottic stenosis, laryngeal webs, subglottic hemangioma, tracheomalacia, congenital tracheal stenosis, laryngotracheal cleft, and tracheal agenesis.

EXIT-to-airway: Fundamentals, prenatal work-up, and technical aspects

Ex-utero intrapartum treatment (EXIT) is a delivery strategy developed to manage a variety of prenatally diagnosed conditions in the transition to newborn life. This procedure allows control and provides time for intervention in otherwise life-threatening malformations, such as congenital upper airway obstructions. EXIT-to-airway has changed the outcome of fetuses with these anomalies. The main purpose of this intervention is to improve the safety of establishing a reliable airway at birth. Maximal but controlled uterine relaxation to maintain feto-maternal perfusion and thus gas exchange, while keeping the fetal and maternal well-being are the paradigms of any type of EXIT. The most important aspect of fetal airway management is to consolidate a highly trained, well-coordinated, multidisciplinary team that is prepared for every contingency. A comprehensive prenatal assessment, including ultrasound, fetal echocardiogram, fetal MRI, and genetic testing is imperative for patient selection. Extensive preoperative planning, ad-hoc team meetings, and surgical simulations for challenging cases are critical strategies to achieve the best outcomes. This article outlines the prenatal work-up, decision making, technical aspects, and principles for a successful EXIT-to-airway procedure.

Tracheal Bronchus and Associated Anomaly Prevalence Among Children.

Background and objectivesTracheal bronchus (TB) is a rare congenital airway anomaly originating from the trachea, with a reported prevalence of 0.9%-3% in children. Although TB was studied in the literature, this anomaly was not evaluated in Qatar. Our study aimed to identify the prevalence and congenital anomalies associated with TB in children in Qatar.DesignIn this descriptive study, we identified patients who underwent flexible bronchoscopy (FB) at two large tertiary centers in Qatar from July 2007 to November 2020. The patients’ demographic, bronchoscopic, and radiologic data were collected. The prevalence of TB and associated congenital anomalies were determined.ResultsOf 1786 patients who underwent FB, 20 (1.12%) were diagnosed with TB. The median age at the time of diagnosis was 31 months (range, 2-154 months). The associated congenital anomalies were identified in 16 cases (80%; p = 0.007). Cardiac defects represent the most common associated anomaly (8/20, 40%).ConclusionThis study revealed that TB is an uncommon airway anomaly and emphasizes its significant association with other congenital malformations. Our findings should alert physicians to other associated TB anomalies and provide timely management when needed.

Abrogation of mesenchyme-specific TGF-β signaling results in lung malformation with prenatal pulmonary cysts in mice.

The TGF-β signaling pathway plays a pivotal role in controlling organogenesis during fetal development. Although the role of TGF-β signaling in promoting lung alveolar epithelial growth has been determined, mesenchymal TGF-β signaling in regulating lung development has not been studied in vivo due to a lack of genetic tools for specifically manipulating gene expression in lung mesenchymal cells. Therefore, the integral roles of TGF-β signaling in regulating lung development and congenital lung diseases are not completely understood. Using a Tbx4 lung enhancer-driven Tet-On inducible Cre transgenic mouse system, we have developed a mouse model in which lung mesenchyme-specific deletion of TGF-β receptor 2 gene (Tgfbr2) is achieved. Reduced airway branching accompanied by defective airway smooth muscle growth and later peripheral cystic lesions occurred when lung mesenchymal Tgfbr2 was deleted from embryonic day 13.5 to 15.5, resulting in postnatal death due to respiratory insufficiency. Although cell proliferation in both lung epithelium and mesenchyme was reduced, epithelial differentiation was not significantly affected. Tgfbr2 downstream Smad-independent ERK1/2 may mediate these mesenchymal effects of TGF-β signaling through the GSK3β-β-catenin-Wnt canonical pathway in fetal mouse lung. Our study suggests that Tgfbr2-mediated TGF-β signaling in prenatal lung mesenchyme is essential for lung development and maturation, and defective TGF-β signaling in lung mesenchyme may be related to abnormal airway branching morphogenesis and congenital airway cystic lesions.

A Review of Tracheal Bronchus in Universiti Kebangsaan Malaysia Medical Centre (UKMMC).

Tracheal bronchus (TB) is a rare congenital anomaly described as a abnormal bronchus that originates directly from the trachea above the carina directed towards the upper lung lobe. We analysed all paediatric rigid endoscopies of the airway from January 2015 until August 2020 to determine the incidence and characteristic of TB. In total, 68 rigid endoscopic airway examination record from children aged 0 to 12years were analyzed. Endoscopic examination was performed from supraglottic region to carina using a 0 degree Hopkins rod lens telescope. Patients with a TB were identified and the site of TB origin was noted. Data of the identified patients was reviewed for the presence of preoperative airway findings such as stridor, upper lobe pneumonia, other congenital anomalies, intraoperative findings and complications and postoperative general condition outcome. TB was detected in 8 (11.8%) of 68 airway endoscopic examinations. 6 children (75%) were syndromic. 5 patients (62.5%) has congenital malacic airway and 2 patients (25%) has congenital tracheal stenosis. All TB originated from the right lateral wall of the trachea. All children had stridor unrelated to TB as presentation and 4 (50%) of children had preoperative upper lobe pneumonia. Tracheal bronchus is not a rare finding and is highly associated with syndromes and other airway anomalies. Although children with TB can be asymptomatic, upper lobe pneumonia is a common presentation. TB should be included in the differential diagnosis in patients with recurrent right upper lobe pneumonia or collapse and patients with unexplained oxygenation problem during endotracheal intubation, particularly in children with syndromes or other congenital anomalies.

Safety and effectiveness of deep sedation in pediatric patients undergoing flexible fibroscopy in spontaneous breathing

Invasive diagnostics and minor surgical procedures with deep sedation on pediatric patients, such as fibroscopic examination, have increased over the past decade. The aim of this study was to evaluate the usefulness and safety of an anesthesiological technique, based on the use of midazolam and ketamine, conducted in spontaneous breathing on a population of pediatric patients with suspected tracheobronchial pathologies. Pediatric patients from birth to 18 years old who underwent sedation diagnostic fibroscopy between April 2018 and March 2019, were enrolled. The anesthesiological technique provided was the intravenous administration of midazolam 0.2 mg/kg and ketamine 2 mg/kg in spontaneous breathing using a face mask with support of O2 and air. Vital signs such as Heart rate (HR), Systolic and Diastolic blood pressure (PAS and PAD) and Arterial oxygen saturation were recorded at the beginning of the procedure, 10 minutes and 30 minutes from the start. Other parameter evaluated were patient’s level of consciousness, quality of the procedure, major and minor complications, adequate recovery of the waking state. Sixteen patients were enrolled, 12 males and 4 females aged between 2 days of life and 7 years. Laryngomalacia tracheomalacia, tracheoesophageal fistula, and congenital airway malformations were the most frequent diseases. As for vital signs: the HR has gone from an average value of 133.4 ± 16.26 bpm at T0 to an average value of 129.3 ± 16.55 bpm at T10 and 133.7 ± 17.35 bpm at T30; PAS and PAD had not significant variations. Among drugs available for the fibroscopic examinations, the combined use of intravenous midazolam 0.2 mg/kg and ketamine 2 mg/kg is safe and well tolerated, reducing the anxiety associated with the examination, without major complications. The current literature is lacking in studies that have included such small and low weight patients. It would be interesting to make a comparison between various sedation techniques in order to identify the safest for the pediatric population.

Airway Challenges in a Preterm Neonate with Undiagnosed Complete Tracheal Rings Posted for Surgery

Preterm neonates are defined as those born before 37 weeks. The anatomical features of preterm neonates vary from that of an adult, such that they have a large tongue, an anterior funnel shaped larynx, angled vocal cords and an omega shaped epiglottis. Their physiological development also differ as they have a greater risk for apnoea of prematurity, airflow obstruction, bronchopulmonary dysplasia, low functional residual capacity and decreased transient oxygen tension. Congenital airway anomalies have a prevalence rate of 0.2-1 in 10,000 live births. Congenital Tracheal Stenosis (CTS) caused by complete tracheal rings is one of the rarest forms of all the airway anomalies that occur, which is characterised by presence of complete ‘O’ shaped cartilaginous rings of trachea devoid of a membranous part. The case discussed in the article is that of a day 26 preterm neonate with increasing abdominal distension and failure to thrive. The neonate was posted for an urgent exploratory laparotomy for abdominal decompression and ileostomy. Patient was kept on Continuous Positive Airway Pressure (CPAP) support for four days immediately after birth; however, intubation was never attempted nor required. With a history of respiratory depression and lack of history of previous intubation, difficult airway cart was kept ready prior to surgery. Supraglottic Airway (SGA) devices were at the core of airway rescue in this case of undiagnosed CTS. This case report shows how and why a preparation for difficult airway in preterm neonates is a necessity. It will provide as a guide if a similar case is encountered by the anaesthetist.

Peak Expiratory Flow Rate in Children with Multiple Neurological Disorder

A neurological disorder is a, structural, biochemical or electrical abnormalities in the brain or spinal cord and peripheral nerves. Neurological disorders include mental retardation, cerebralpalsy, autism and down’ syndrome. Children with neurological disorders have a high incidence of respiratory problems. Many children with cerebral palsy have scoliosis, an irregular curvature of spine that can interfere with lungs ability to expand. Genetic condition including cerebral palsy and muscular dystrophy can be associated with congenital airway abnormalities. The aim of the study is to find out peak expiratory flow rate in children with multiple neurological disorder. Study design non-experimental,15 subjects with age group of 7-17years was selected based on the inclusion and exclusion criteria.(subjects:3-cerebral palsy,3-down syndrome,2-autism,7-mental retardation) were selected Maithree special school, East Tambaram. An informed consent was obtained from the parents and children with detailed explanation of the procedure. First the participant was asked to breath in and breath out normally and then breath in deeply as much as possible followed by quick expiration to the maximum into the device. Three trials have been done and best of the three is adopted as PEFR. The value on the meter was monitored and recorded. The training was stopped whenever the subject feels dizziness. The data on height, age, sex, weight, were registered. The peak expiratory flow rate of normal children ranges from 182-565 l/min.The mean value of PEFR in children with multiple neurological disorder was found to be cerebral palsy-121 l/ min, Down’s syndrome-130 l/min, autism-77.5 l/min, mentally retarded-145 l/min. For the data, complete action of PEFR measurement were performed in children with multiple neurological disorder. The PEFR values clearly depicts that the children with multiple neurological disorder have decreased PEFR. Our findings confirm that the peak expiratory flow meter is a well functioning instrument for measuring PEFR in children, giving reliable results, and an inexpensive tool. The study conclude that there was a decreased PEFR in children with cerebral palsy, down’s syndrome, autism and mentally retarded. The study was made simple and this can be done by giving interventions like respiratory muscle training.

Small sleepers, big data: leveraging big data to explore sleep-disordered breathing in infants and young children.

Infants represent an understudied minority in sleep-disordered breathing (SDB) research and yet the disease can have a significant impact on health over the formative years of neurocognitive development that follow. Herein we report data on SDB in this population using a big data approach. Data were abstracted using the Cerner Health Facts database. Demographics, sleep diagnoses, comorbid medication conditions, healthcare utilization, and economic outcomes are reported. In a cohort of 68.7 million unique patients, over a 9-year period, there were 9,773 infants and young children with a diagnosis of SDB (obstructive sleep apnea [OSA], nonobstructive sleep apnea, and "other" sleep apnea) who met inclusion criteria, encompassing 17,574 encounters, and a total of 27,290 diagnoses across 62 U.S. health systems, 172 facilities, and 3 patient encounter types (inpatient, clinic, and outpatient). Thirty-nine percent were female. Thirty-nine percent were ≤1 year of age (6,429 infants), 50% were 1-2 years of age, and 11% were 2 years of age. The most common comorbid diagnoses were micrognathia, congenital airway abnormalities, gastroesophageal reflux, chronic tonsillitis/adenoiditis, and anomalies of the respiratory system. Payor mix was dominated by government-funded entities. We have used a novel resource, large-scale aggregate, de-identified EHR data, to examine SDB. In this population, SDB is multifactorial, closely linked to comorbid medical conditions and may contribute to a significant burden of healthcare costs. Further research focusing on infants at highest risk for SDB can help target resources and facilitate personalized management.

Congenital Absence of Tracheal or Bronchial Rings.

Congenital airway stenosis secondary to absent tracheal or bronchial rings is a rare congenital anomaly that is difficult to manage both clinically and surgically. This typically manifests as severe segmental tracheomalacia, and only isolated cases with short-term follow-up have been previously described. We aim to describe a series of children with absent tracheal or bronchial rings who underwent surgical management and had long-term follow-up. Case series with chart review. Tertiary care pediatric hospital. Patients with absent tracheal or bronchial rings from 2002 to 2016. Electronic and paper medical records were queried to obtain demographics, age at diagnosis and surgery, pre- and postoperative symptoms, location of absent rings, procedure performed, length of follow-up, and adjunctive procedures performed. Nine subjects were identified who underwent slide tracheoplasty for correction of congenital absent tracheal or bronchial rings. Age at diagnosis ranged from 10 days to 5 years of age (median, 4 weeks). Age at surgery ranged from 3 weeks to 5 years of age (median, 5 weeks). Six out of 9 subjects were extubated on postoperative day 1. Only 1 subject required additional intervention, which included balloon dilation, tracheobronchial stenting, and aortopexy to alleviate the obstruction. Mean follow-up time was 5.89 years. This is the largest series of children with absent tracheal rings who underwent slide tracheoplasty with long-term follow-up presented to date. Slide tracheoplasty is an effective surgical intervention for the treatment of absent tracheal or bronchial rings in infants and young children.

Anesthetic management of pulmonary surgery in newborns and infants.

The main congenital pulmonary airways malformations in newborns and infants requiring surgery are cystic adenoid malformation, congenital lobar emphysema and bronchogenic cyst. The surgical treatment preferably via thoracoscopy is recommended within the first year of life to avoid the risk of pneumopathy. A monopulmonary ventilation is then required by the surgeon to operate the diseased lung. The anesthetic management of intraoperative mono-pulmonary ventilation in newborns and infants is always challenging for the anesthesiologist. The main objective of this study was to describe anesthetic protocol for thoracoscopy and variations of monitored parameters during a mono-pulmonary ventilation procedure in newborns and infants.

Airway Abnormalities in Patients With Congenital Heart Disease: Incidence and Associated Factors

Airway abnormalities complicate the perioperative course of patients with congenital heart disease (CHD), leading to significant morbidity and mortality. The literature describing airway abnormalities in those patients is scarce. This study aimed to determine the incidence of airway abnormalities in CHD patients and identify associated factors, genetic syndromes, and cardiac diagnoses. Retrospective study conducted after institutional review board approval. Tertiary children's hospital. Patients presenting for cardiac diagnostic, interventional, or surgical procedures from 2012 to 2018. A total of 9,495 encounters were reviewed. age >18 years. Methods/Interventions: Age, weight, sex, intubation technique, number of intubation attempts, and difficult intubation (DI) were recorded. Using the International Classification of Diseases, Ninth and Tenth Revisions codes, genetic syndromes, acquired and congenital airway abnormalities, and cardiac diagnoses were identified. Multivariate generalized estimating equations modeling was used to identify independent predictors of airway abnormalities. A total of 4,797 patients, with 8,657 encounters were included. The median age was 1.3 years (interquartile range [IQR]: 0.2-6.0) and weight was 9.2 kg (IQR: 4.3-19.2), and 55% were male. A total of 16.7% had at least 1 genetic syndrome; 8.5% had congenital airway abnormalities and 9.7% acquired. Incidence of DI was 1.1%. The most common syndromes were Down, 22q11.2 microdeletion, and CHARGE. The most frequent congenital airway abnormalities were laryngomalacia and bronchomalacia, and the most frequent acquired were partial and total vocal cord paralysis. The likelihood of a coexistent airway abnormality should be considered in premature CHD patients, weight <10 kg, and in those with specific cardiac lesions and a concomitant genetic syndrome. Preoperative identification of patients at high risk of airway abnormalities is useful in planning their perioperative airway management.

Exploring respiratory syncytial virus prophylaxis for children with all grades of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is an independent risk factor for respiratory syncytial virus (RSV) hospitalisation in children who have not received prophylaxis. It is associated with an RSV hospitalisation rate of 12%-21%, which is up to 10 times higher than term-born infants and other high-risk groups without comorbidities, even up to three years of age.1 A meta-analysis has confirmed that hospitalised children with BPD experience significant morbidity compared to non BPD subjects including a median hospital length of stay of 7.2 days versus 2.5 days. They also need higher intensive care admissions, with an odds ratio (OR) of 2.9 and 95% confidence interval (CI) of 2.3-3.5 (p < 0.001), have a greater need for mechanical ventilation (OR 8.2, 95% CI, 7.6-8.9, p < 0.001) and experience a higher case-fatality (OR 12.8, 95% CI 9.4-17.3, p< 0.001).2 In 2012, expenditure for children hospitalised with RSV and BPD, in the USA, was 1.7-fold higher than children hospitalised with congenital heart disease and airway anomalies.

Prematurity and associated future paediatric airway pathology: experience from a single tertiary paediatric ENT centre.

Enhanced management of the pre-term patient has resulted in improved survival rates in increasingly premature patients. Although prematurity predisposes to congenital airway pathology, there is also increased risk of endotracheal intubation, and therefore acquired subglottic pathology. We sought to evaluate airway pathology in children outside the neonatal period with a history of prematurity to explore the relationship between prematurity and upper airway pathologies. Data for patients undergoing elective microlaryngobronchoscopy (MLB) at our centre were collected prospectively over a 5-year period. Patients identified as premature were sub-classified by the grade of prematurity. 339 patients over 1month of age underwent MLB, of which 56 (16.5%) were born prematurely. Of those with identified airway pathology, 49 (23.4%) were born prematurely, accounting for 32.6% of subglottic stenosis (n = 30), 24% of laryngomalacia (n = 13) and 19% of laryngeal cleft diagnoses (n = 16). 49 premature patients (87.5%) had one or more airway pathologies diagnosed. Multi-level airway pathology was seen in twelve premature infants (21.4%), demonstrating a statistically significant association (odds ratio 3.396; 95% CI 1.697-6.842; p value < 0.0016). Incidence of airway pathology, the severity of airway disease and multi-level airway pathology were not related to the grade of prematurity. Premature patients account for a significant proportion of the workload within our tertiary centre due to improving neonatal care and survival in pre-term infants. We suggest early paediatric ENT evaluation for ex-premature patients with symptoms of airway pathology, with a low threshold for MLB. Improving neonatal survival rates in ever-increasing prematurity will require the further provision of specialist paediatric ENT services to manage their ongoing care.

IL-5 Exposure In Utero Increases Lung Nerve Density and Airway Reactivity in Adult Offspring.

Asthma is characterized by airway hyperreactivity and inflammation. In the lungs, parasympathetic and sensory nerves control airway tone and induce bronchoconstriction. Dysregulation of these nerves results in airway hyperreactivity. Humans with eosinophilic asthma have significantly increased sensory nerve density in airway epithelium, suggesting that type 2 cytokines and inflammatory cells promote nerve growth. Similarly, mice with congenital airway eosinophilia also have airway hyperreactivity and increased airway sensory nerve density. Here, we tested whether this occurs during development. We show that transgenic mice that overexpress IL-5, a cytokine required for eosinophil hematopoiesis, give birth to wild-type offspring that have significantly increased airway epithelial nerve density and airway hyperreactivity that persists into adulthood. These effects are caused by in utero exposure to maternal IL-5 and resulting fetal eosinophilia. Allergen exposure of these adult wild-type offspring results in severe airway hyperreactivity, leading to fatal reflex bronchoconstriction. Our results demonstrate that fetal exposure to IL-5 is a developmental origin of airway hyperreactivity, mediated by hyperinnervation of airway epithelium.