Structural Airway Abnormalities Research Articles

Fetal Origins of Asthma: A Longitudinal Study From Birth to Age 36 Years

To determine the relationship between the low percentage of expiratory time necessary to reach tidal expiratory flow (tPTEF/tE) and flow at the end tidal point (VmaxFRC) in early infancy to the development of asthma, airflow limitation, and airway structural abnormalities in this 36-year birth cohort of the Tucson Children’s Respiratory Study.This is a birth cohort consisting of 1246 healthy infants born between 1980 to 1984 enrolled in the TCRS. Only 180 infants <6 months of age were tested by using the chest compression technique for pulmonary function testing because this technique was not developed until the end of the enrollment period.Demographic information was obtained via parent completed questionnaires. Infant lung function testing included tidal breathing indices, functional residual capacity via a helium-dilutions-gas-equilibration method, and partial expiratory-flow curves, from which the tPTEF/tE was determined. VmaxFRC was determined via partial expiratory flow-volume curves by using the chest compression technique. Active asthma was defined as a physician diagnosis of asthma at any age, with active symptoms within the previous year based on questionnaires obtained every 2 to 4 years between the ages of 6 and 36 years. Survey information, spirometry (prebronchodilator and postbronchodilator and full lung volumes), and high-resolution computed tomography of the chest was completed at the age of 26 years. Data were analyzed via multivariate linear regression models and generalized estimating equations.A total of 180 infants, who underwent pulmonary function testing, were compared with 1066 participants who did not undergo testing. The tested cohort revealed 8% with active asthma at the age of 6 years and 18% at the age of 36 years. Levels of infant tPTEF/tE and VmaxFRC were lower for participants who developed active asthma. tPTEF/tE and VmaxFRC were associated with a significant risk for active asthma (P = .003 and P =.007, respectively) and those in the lowest tertile of both indices were at highest risk (P = .009 and P = .01, respectively). Both tPTEF/tE and VmaxFRC were associated with an increased odds of developing active asthma between the ages of 6 and 36 years (70% [P = .001] and 55% [P = .005], respectively). At the age of 26 years, low infant tPTEF/tE was associated with reductions in airway diameter, total area, and luminal and wall areas, whereas VmaxFRC was associated with reduced forced expiratory volume in 1 second to forced vital capacity, forced expiratory volume in 1 second, and forced expiratory flow 25% to 75% levels.Reduced tPTEF/tE and VmaxFRC levels in infancy may indicate an increased risk for active asthma by the age of 36 years on the basis of pulmonary function testing and airway imaging in adulthood.Recognizing risk factors for asthma may extend beyond family history and personal history of atopy and respiratory infections. This study reveals that airflow limitation early in infancy may help predict asthma later in life and warrants further studies to standardize methods for clinical use and application. Understanding the time course of asthma development is essential in prevention and treatment.

The Precision Interventions for Severe and/or Exacerbation-Prone (PrecISE) Asthma Network: An overview of Network organization, procedures, and interventions

Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation-prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. A current challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here, we describe the Precision Interventions for Severe and/or Exacerbation-Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the United States. The PrecISE Network was designed to conduct phase II/proof-of-concept clinical trials of precision interventions in the population with severe asthma, and is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the PrecISE Network will evaluate up to 6 interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the PrecISE Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for severe asthma.

Middle ear disease requiring myringotomy in the first two years after tracheotomy in the pediatric population

ObjectivesRisk factors for middle ear disease necessitating myringotomy with tympanostomy tube placement after a tracheostomy have not been thoroughly explored. This study investigates the incidence and risk factors for ear tube placement in pediatric patients with a tracheostomy. MethodsPediatric patients under age 18 who underwent tracheotomy between 2002 and 2010 at two institutions were identified. Patients were excluded if they had undergone myringotomy prior to, or at the same time as, the tracheotomy, or did not have at least two years of follow-up clinic visits. The presence of other comorbidities was recorded. Descriptive statistics and logistic regression models were used to assess the impact of clinical characteristics on outcomes. ResultsA total of 214 patients met inclusion criteria. Median patient age at time of tracheotomy was 6 months (IQR 2–17), median patient age at time of myringotomy with tubes was 12 months (IQR8-17), and median time between tracheotomy and myringotomy with tube placement was 8 months (IQR 5–11). Sixty-seven (31%) patients required myringotomy with tympanostomy tube placement within the first two years after tracheotomy. Fifty-eight (87%) patients who underwent myringotomy with tympanostomy tubes were younger than 2 years at the time of the procedure. Logistical regression found younger age at time of tracheotomy to be a risk factor (OR: 0.71, 95% CI: 0.5–0.9, p < 0.006). The combination of tracheostomy with gastric tube increased the risk of requiring myringotomy with tubes 2.79 fold (p < 0.009). Craniofacial abnormalities (p < 0.001), known genetic syndrome (p = 0.009), cleft palate (p < 0.001), age at time of tracheotomy (p < 0.001) and gastric tubes (p = 0.002) were all independently found to increase risk of myringotomy with tubes. Patients’ gestational age (p = 0.411), ventilator dependence (p = 0.33), and airway structural abnormalities (p = 0.632) did not increase this risk. ConclusionThis study reports a high incidence of myringotomy with tubes in children with tracheostomy relative to the general pediatric population. Many comorbid conditions that often accompany the need for tracheotomy place these patients at a higher risk for ear disease requiring surgical intervention. Risk factors for operative middle ear disease in this population included age at time of tracheostomy, craniofacial abnormalities, and presence of a G-tube.

852 Severe Central Sleep Apnea in a Patient with Cornelia de Lange Syndrome

Abstract Introduction Cornelia de Lange syndrome (CdLS) is a rare multisystem disorder with characteristic facial dysmorphisms, upper airway structural abnormalities, and varying degrees of intellectual and neurologic deficits. Affected patients can have many sleep problems including chronic insomnia and obstructive sleep apnea; however, there is no literature indicating central sleep apnea as a common sleep disorder in this patient population. We describe a patient with CdLS with an unusual presentation of both severe obstructive and central sleep apnea. Report of case(s) The patient is a 12-year-old female with CdLS, global developmental delay, repaired bilateral cleft-palate, and oropharyngeal dysphagia. She was referred for diagnostic polysomnography for evaluation of snoring. Physical examination findings were significant for distinctive features of the head and face including microcephaly, micrognathia, and synophrys. Neurologically, the patient was non-verbal and wheelchair bound. Pre-evaluation screening indicated no concerns from the caregiver regarding problems with sleep initiation, maintenance, or daytime symptoms. Polysomnography (PSG) at age 7 years revealed severe obstructive and central sleep apnea with an apnea-hypopnea index (AHI) of 78.2/hr. The majority of these were central events (68.44/hr). There were no epileptiform foci recorded. Bilevel Positive Airway Pressure (BPAP) in Spontaneous/Timed (S/T) mode was titrated during the study which resolved all central events. Magnetic resonance imaging of the brain was obtained indicating mild hypoplasia of the corpus callosum. Since the initial PSG, 5 additional routine studies were conducted and progressive worsening of central sleep apnea was noted with the highest recorded AHI of 108.8/hr (central events: 81.4/hr). Apneic events were fairly managed with BPAP in ST mode. Conclusion Sleep-disordered breathing in CdLS is an increasingly diagnosed entity. While previous literature indicates airway obstruction as a common cause for sleep apnea in children with CdLS, our case suggests that clinicians should consider central causes of sleep apnea in these patients. Given the sub-clinical progression of sleep apnea in this case study, routine follow up PSGs should be considered. Further research is necessary to increase knowledge of the incidence and management of central sleep apnea in children with CdLS. Support (if any):

821 An Unusual Pediatric PAP Compliance Obstacle, Even When the Mask Fits

Abstract Introduction Proper mask fitting is an important factor for compliant and effective use of PAP therapy. However, we present 2 patients whose masks became a barrier to PAP therapy despite a well-fitting mask. Report of case(s) Case 1 A 12-year-old female with ADHD, Chiari I malformation status-post decompression, and persistent mixed central and obstructive sleep apnea is managed with BPAP S/T. Despite absence of upper airway structural abnormalities, she is a mouth-breather during sleep and only tolerates full face masks. Despite ensuring a good mask fit and optimal BPAP settings to control her AHI, she sleeps with her neck hyperextended, resulting in her lower jaw pushing caudally and the mask liner slipping into her mouth. This stimulated chewing and resulted in damage to several masks. Case 2 An 8-year-old male with congenital central hypoventilation syndrome is managed with BPAP S/T during sleep. Similar to case 1, he is a mouth-breather during sleep and can only tolerate full face masks. Although his mask and headgear fit him well, he drools in sleep which results in the silicone liner slipping into his mouth, stimulating chewing. This has led to the need for replacement of several masks. Of note, drooling did not occur when he was previously using assisted ventilation via tracheostomy, and bruxism was not identified during polysomnography. Conclusion To our knowledge, this is the first report of PAP mask chewing, thus its incidence is unknown. We suspect that the mask liner slipping into the mouth touches the anterior surfaces of the teeth stimulating the chewing reflex. The frequency of mask chewing and consequent damage is unpredictable and often necessitates mask replacement. Insurance companies should consider this unique mask complication when determining their mask coverage policies since the typical 6-months interval for authorization of a new mask can impair the patient’s health, PAP compliance, and become an out-of-pocket financial burden for families. Although it did not occur in our patients, mask chewing may pose a potential choking hazard. Awareness of mask chewing may help in improving pediatric PAP mask development to ensure masks are safe. Support (if any):

High eosinophil counts predict decline in FEV1: results from the CanCOLD study.

The aim of this study was to examine the association between blood eosinophil levels and the decline in lung function in individuals aged >40 years from the general population. The study evaluated the eosinophil counts from thawed blood in 1120 participants (mean age 65 years) from the prospective population-based Canadian Cohort of Obstructive Lung Disease (CanCOLD) study. Participants answered interviewer-administered respiratory questionnaires and performed pre-/post-bronchodilator spirometric tests at 18-month intervals; computed tomography (CT) imaging was performed at baseline. Statistical analyses to describe the relationship between eosinophil levels and decline in forced expiratory volume in 1 s (FEV1) were performed using random mixed-effects regression models with adjustments for demographics, smoking, baseline FEV1, ever-asthma and history of exacerbations in the previous 12 months. CT measurements were compared between eosinophil subgroups using ANOVA. Participants who had a peripheral eosinophil count of ≥300 cells·µL-1 (n=273) had a greater decline in FEV1 compared with those with eosinophil counts of <150 cells·µL-1 (n=430; p=0.003) (reference group) and 150-<300 cells·µL-1 (n=417; p=0.003). The absolute change in FEV1 was -32.99 mL·year-1 for participants with eosinophil counts <150 cells·µL-1; -38.78 mL·year-1 for those with 150-<300 cells·µL-1 and -67.30 mL·year-1 for participants with ≥300 cells·µL-1. In COPD, higher eosinophil count was associated with quantitative CT measurements reflecting both small and large airway abnormalities. A blood eosinophil count of ≥300 cells·µL-1 is an independent risk factor for accelerated lung function decline in older adults and is related to undetected structural airway abnormalities.

Fetal Origins of Asthma: A Longitudinal Study from Birth to Age 36 Years.

Rationale: Deficits in infant lung function-including the ratio of the time to reach peak tidal expiratory flow to the total expiratory time (tptef/te) and maximal expiratory flow at FRC (V̇maxFRC)-have been linked to increased risk for childhood asthma.Objectives: To examine the individual and combined effects of tptef/te and V̇maxFRC in infancy on risk for asthma and abnormalities of airway structure into mid-adult life.Methods: One hundred eighty participants in the Tucson Children's Respiratory Study birth cohort had lung function measured by the chest-compression technique in infancy (mean age ± SD: 2.0 ± 1.2 mo). Active asthma was assessed in up to 12 questionnaires between ages 6 and 36 years. Spirometry and chest high-resolution computed tomographic (HRCT) imaging were completed in a subset of participants at age 26. The relations of infant tptef/te and V̇maxFRC to active asthma and airway structural abnormalities into adult life were tested in multivariable mixed models.Measurements and Main Results: After adjustment for covariates, a 1-SD decrease in infant tptef/te and V̇maxFRC was associated with a 70% (P = 0.001) and 55% (P = 0.005) increased risk of active asthma, respectively. These effects were partly independent, and two out of three infants who were in the lowest tertile for both tptef/te and V̇maxFRC developed active asthma by mid-adult life. Infant V̇maxFRC predicted reduced airflow and infant tptef/te reduced HRCT airway caliber at age 26.Conclusions: These findings underscore the long-lasting effects of the fetal origins of asthma, support independent contributions by infant tptef/te and V̇maxFRC to development of asthma, and link deficits at birth in tptef/te with HRCT-assessed structural airway abnormalities in adult life.

Pulmonary function evaluation in pediatric patients with primary immunodeficiency complicated by bronchiectasis.

Primary immunodeficiency (PID) accompanying with recurrent respiratory infections is thought to have a devastating effect on lung function. However, the associations between the airway structural abnormalities on chest computed tomography (CT), severity of dyspnea, and deterioration of pulmonary function test (PFT) have not been fully addressed. Children diagnosed with PID in a tertiary referred center in northern Taiwan were enrolled. Demographic and clinical data including age, sex, age at diagnosis of PID, and follow-up period were collected. Chest CT images (modified Reiff scores), parameters of PFT, and life quality questionnaires (mMRC dyspnea scale) were analyzed and correlated using Spearman's rank correlation test. A total of nineteen children with PID were enrolled and thirteen patients were diagnosed as having bronchiectasis based on chest CT scans. Modified Reiff scores of chest CT scan were negatively correlated with FEV1 (% predicted) and FEV1/FVC ratio (P<0.05). A strongly negative correlation was found between the mMRC dyspnea scale and FEV1 (% predicted) and FVC (% predicted), but positively correlated with RV (% predicted) and RV/TLC ratio (P<0.05). Furthermore, there was a negative correlation between FVC (% predicted) with increasing follow-up period (P<0.05). In pediatric patients with PID, chest CT scan appears to be a good tool for not only the diagnosis of bronchiectasis, but also the degree of pulmonary function impairment. Further quality of life impairments could be particularly due to the airflow obstruction and air trapping related to bronchiectasis.

Airway Remodeling and Bronchodilator Responses in Asthma Accessed by Endobronchial Optical Coherence Tomography

Background: Asthma is characterized by chronic airway inflammation and remodeling. Understanding airway structural changes and the bronchodilator responses may help unravel targets for intervention. However, structural abnormalities of asthmatic airways with different disease severity and the major anatomical site of bronchodilator responses have not been well elucidated. Methods: We recruited 104 asthmatic patients (when clinically stable) and 31 non-smoking control subjects to compare the airway inner area (Ai) and airway wall area percentage (Aw%) with endobronchial optical coherence tomography. We also enrolled 32 patients with moderate-to-severe asthma to dynamically access the airway morphological changes after salbutamol inhalation. Findings: More prominent airway structural abnormalities correlated with greater asthma severity, evidenced by the decreased Ai and greater Aw% in medium-sized and small airways. Patients with mild asthma yielded comparable Ai but greater Aw% than control subjects. A longer disease duration correlated with lower Ai and greater Aw% from the 3rd to 6th generation of bronchi. Salbutamol inhalation led to a rapid dilatation of both medium-sized and small airways, the lung function improvement correlated significantly with the increase in Ai of the medium-sized, but not small, airways at 15 min. Interpretation: Luminal narrowing and airway wall thickening of the medium-sized and small airways are present in mild asthma and reflect asthma severity, lending support to the use of anti-imflammatory intervention in mild asthma. The medium-sized airways are the crucial site of the bronchodilator responses, providing the scientific rationale for future development of more effective delivery of inhaled medications for asthma. Funding Statement: National Natural Science Foundation of China (No.81770017), National Natural Science Foundation of China (No.81900032), Pearl River S&T Nova Program of Guangzhou No. 201710010097 and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme 2017 Declaration of Interests: Prof. Li declared that he had received the National Natural Science Foundation of China (No.81770017). Dr Su declared that he had received the National Natural Science Foundation of China (No.81900032). Prof. Guan declared that he had received Pearl River S&T Nova Program of Guangzhou No. 201710010097, and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme 2017. All other authors declared no potential conflict of interest. None of the funding sources had any role on the study Ethics Approval Statement: This study was approved by the Ethics Committee of The First Affiliated Hospital of Guangzhou Medical University (Medical Ethics [Year 2014] No. 51 and [Year 2019] No. K09). All subjects gave written informed consent.

Airway Anomalies in Patients With 22q11.2 Deletion Syndrome: A 5-Year Review.

To characterize the frequency of airway anomalies in patients with 22q11.2 deletion syndrome (22q11DS). Retrospective review of patients with 22q11DS who had undergone microlaryngoscopy/bronchoscopy (MLB) for aerodigestive symptoms at a tertiary care children's hospital from 2011 to 2016. Thirty patients underwent an MLB due to the following indications: aspiration (11), stridor (10), chronic respiratory failure due to ventilator dependence (8), and difficult intubation (1). Median age at MLB was 6.5 months (range, 0.25-32 months). Forty airway anomalies were identified in 20 (66%) patients. Laryngomalacia (10), tracheomalacia (8), and bronchomalcia (8) were the most common intraoperative findings, followed by laryngeal cleft (5), anterior glottic web (5), subglottic stenosis (3), and subglottic cysts (1). Synchronous airway anomalies were common and identified in 11 (55%) of the patients who had identified anomalies on MLB. Nineteen of the 20 patients required operative intervention due to the anomalies identified. Structural airway abnormalities are common in children with 22q11DS undergoing MLB, and synchronous anomalies can frequently exist. Providers caring for children with 22q11DS should be vigilant about airway evaluation when aerodigestive symptoms are present.

All plugged up - noninvasive mucus score to assess airway dysfunction in asthma.

Asthma is remarkably heterogeneous, and there are multiple underlying inflammatory pathways and structural airway abnormalities that lead to symptomatic disease. Consequently, a current challenge in the field is to precisely characterize different types of asthma, with the goal of developing personalized approaches to therapy. In the current issue of the JCI, Dunican et al. developed a noninvasive way to assess airway dysfunction in asthma by measuring mucus accumulation using multidetector computed tomography (MDCT) and found that mucus plugging of small airways was remarkably common in subjects with severe asthma. This work highlights the importance of noninvasive imaging approaches in defining specific asthma subsets and guiding targeted therapies.

Structural airway abnormalities contribute to dysphagia in children with esophageal atresia and tracheoesophageal fistula

BackgroundLong-term dysphagia occurs in up to 50% of repaired esophageal atresia and tracheoesophageal fistula (EA/TEF) patients. The underlying factors are unclear and may include stricture, esophageal dysmotility, or associated anomalies. Our purpose was to determine whether structural airway abnormalities (SAA) are associated with dysphagia in EA/TEF. MethodsWe conducted a retrospective chart review of children who underwent EA/TEF repair in our hospital system from 2007 to 2016. Children with identified SAA (oropharyngeal abnormalities, laryngeal clefts, laryngomalacia, vocal cord paralysis, and tracheomalacia) were compared to those without airway abnormalities. Dysphagia outcomes were determined by the need for tube feeding and the modified pediatric Functional Oral Intake Scale (FOIS) at 1 year. ResultsSAA was diagnosed in 55/145 (37.9%) patients with EA/TEF. Oropharyngeal aspiration was more common in children with SAA (58.3% vs. 36.4%, p=0.028). Children with SAA were more likely to require tube feeding both at discharge (79.6% vs. 48.3%, p<0.001) and at 1 year (52.7% vs. 13.6%, p<0.001) and had lower mean FOIS (4.18 vs. 6.21, p<0.001). In the logistic regression model adjusting for gestational age, long gap EA, and esophageal stricture, the presence of SAA remained a significant risk factor for dysphagia (OR 4.17 (95% CI 1.58–11.03)). ConclusionSAA are common in children with EA/TEF and are associated with dysphagia, even after accounting for gestational age, esophageal gap and stricture. This study highlights the need for a multidisciplinary approach, including early laryngoscopy and bronchoscopy, in the evaluation of the EA/TEF child with dysphagia. Level of evidenceLevel II retrospective prognostic study

Low rate of positive bronchoscopy for suspected foreign body aspiration in infants

ObjectivesTo describe our institution's low rate of positive bronchoscopy in infants suspected of inhaling a foreign body. Study DesignRetrospective chart review. MethodsA retrospective review was performed of patients at a tertiary children's hospital with suspected inhalation of a foreign body. Charts were reviewed for demographic information, radiologic findings, operative reports, and respiratory viral panels were reviewed. ResultsSixteen pediatric patients under 12 months of age were identified from 2008 to 2016 with a diagnosis of possible airway foreign body inhalation who underwent emergent bronchoscopy. Of these patients, only one was positive for a foreign body present in the airway. The remaining 15 children were found to have a negative direct laryngoscopy and bronchoscopy evaluation for a foreign body. Of these fifteen patients, 14 were found to have structural airway abnormalities and 7 tested positive for a respiratory viral infection. ConclusionsOur institution has a low rate of positive bronchoscopy for highly suspected foreign body inhalation in a group of patients less than 12 months of age. Patients presenting with respiratory distress, stridor, or other airway symptoms were often found to have an underlying airway abnormality or viral infection, which coupled with an unclear history, would increase the suspicion for an airway foreign body and subsequent decision to perform bronchoscopy. In stable patients, diagnostic evaluation for an underlying respiratory infection should be performed in these cases. Level of EvidenceCase Series.

Association of airway abnormalities with 22q11.2 deletion syndrome

Introduction22q11.2 deletion syndrome (22q11.2DS) presents with complex but variable symptoms, including cardiac, immune, palatal, endocrine, cognitive, and psychiatric issues. However, an association of 22q11.2DS with structural airway abnormalities has not been formally described. The aim of this study was to document the frequency of this association. MethodsWe retrospectively reviewed medical records of patients with 22q11.2DS evaluated in the 22q and You Center at the Children's Hospital of Philadelphia between 1999 and 2015 referred to otolaryngology for an airway assessment. Type of airway abnormality and presence of comorbidities, such as congenital heart disease, tracheostomy, and association with prenatal symptomatology such as polyhydramnios, were noted. ResultsOf the 104 patients who underwent an otolaryngology procedure (microlaryngoscopy or bronchoscopy), 71% (n = 74) had airway abnormalities. Patients with airway abnormalities ranged in age from 5 months to 37 years, with similar prevalence among males and females. Observed airway abnormalities included tracheomalacia (36%), subglottic stenosis (28%), laryngomalacia (26%), glottic web (21%), and bronchomalacia (16%). Most patients with airway abnormalities (91%) had an associated congenital heart defect, with ventricular septal defect and Tetralogy of Fallot being the most prevalent. Importantly, 30% of patients required a tracheostomy, and overall polyhydramnios was noted in 16% of pregnancies. ConclusionAirway abnormalities are a common feature of 22q11.2DS, leading to substantial morbidity, particularly when combined with complex cardiac disease. Polyhydramnios may be an important prenatal clue to both the diagnosis of 22q11.2DS and airway anomalies. Postnatal assessment of airway structure and function among patients with 22q11.2DS is an important component of overall evaluation and will help guide long-term management.

A rare case of co-existing Treacher-Collins and Down syndrome

Abstract Both Treacher-Collins (TCS) and Down syndrome cause structural and functional airway abnormalities. We present the case of a neonate with both syndromes who required tracheostomy in the first hour of life due to severe upper airway obstruction. The co-occurrence of both syndromes is rare, and presents unique challenges in securing the airway in the perinatal period.

Early Airway Structural Changes in Cystic Fibrosis Pigs as a Determinant of Particle Distribution and Deposition

The pathogenesis of cystic fibrosis (CF) airway disease is not well understood. A porcine CF model was recently generated, and these animals develop lung disease similar to humans with CF. At birth, before infection and inflammation, CF pigs have airways that are irregularly shaped and have a reduced caliber compared to non-CF pigs. We hypothesized that these airway structural abnormalities affect airflow patterns and particle distribution. To test this hypothesis we used computational fluid dynamics (CFD) on airway geometries obtained by computed tomography of newborn non-CF and CF pigs. For the same flow rate, newborn CF pig airways exhibited higher air velocity and resistance compared to non-CF. Moreover we found that, at the carina bifurcation, particles greater than 5-μm preferably distributed to the right CF lung despite almost equal airflow ventilation in non-CF and CF. CFD modeling also predicted that deposition efficiency was greater in CF compared to non-CF for 5- and 10-μm particles. These differences were most significant in the airways included in the geometry supplying the right caudal, right accessory, left caudal, and left cranial lobes. The irregular particle distribution and increased deposition in newborn CF pig airways suggest that early airway structural abnormalities might contribute to CF disease pathogenesis.

Obliterative lower airway lesions in childhood: Bronchoscopic diagnosis and clinical spectrum

Previous reports have described structural airway abnormalities in children with non-cystic fibrosis chronic supportive lung disease as well as obliterative membranes in the major bronchi of cystic fibrosis patients. The putative paradigm proposed in the evolution of these membranes invokes intense inflammation resulting in granulation tissue and neovascularization with the formation of pyogenic granuloma and eventually fibrosis. Our series of four cases widens the spectrum of conditions that may be conducive to large airway obliteration to include non-suppurative chronic infections and possibly immunosuppression. Obliteration of lumina in proximal and distal airways was visualized on bronchoscopy, the latter by the use of the ultrathin bronchoscopes. An attempt at invasive intervention by transbronchial breaching of the obstruction was unsuccessful in three cases, and in one case, the obliterative process resolved spontaneously and without any radiologic trace, presumably by resorption or rupture or through development of collateral ventilation. This series highlights the use of bronchoscopy for diagnosis and occasionally for therapeutic intervention in hitherto little recognized obliterative airway lesions. These acquired obliterative lesions should be considered in the evaluation of patients with isolated non-resolving pulmonary infiltrates or other conditions in which bronchial and bronchiolar patency may be impaired.

Etiology of laryngeal stridor in 297 cases of infants

Objective To summarize the cause of laryngeal stridor in infants in order to make accurate diagnosis and treatment of the disease.Methods We reviewed medical records of 297 cases of patients less than 3 year of age with the presenting symptom of stridor who were initially evaluated in the outpatient setting of otorhinolaryngological department from Jan 2005 to Jan 2010.The causes of stridor were clarified by examinations of ultrafine electronic laryngoscope,throat three-dimensional CT,and bronchoscopy in all cases.Patients underwent history-taking,physical examination and flexible laryngoscopy,CT examination or bronchoscopy evaluation in the operating room.Results Of all 297 patients,199 cases ( 67.0％ ) were diagnosed as congenital airway abnomalities for cause of stridor,which included congenital laryngeal abnomalities in 169(84.9％,169/199) and congenital tracheal abnormalities in 30 cases( 15.1％,30/199).Another 98 cases (33.0％,98/297) were diagnosed as acquired disease for cause of stridor.The most congenital laryngeal anomaly was laryngomalacia ( 159,94.1％,159/169 ).The most congenital tracheal abnormalities was tracheomalacia ( 14,46.7％,14/30 ).Sixty-four cases ( 65.3％,64/98 ) were diagnosed as foreign body in airway and 26 cases (26.5％,26/98) were respiratory infection,which were the first and second most common causes of acquired disease for stuidor.Conclusion Congenital airway structural abnormalities as a major cause of infant laryngeal stridor,followed by acquired disorders,including airway foreign body and infection. Key words: Laryngeal stridor; Laryngomalacia; Airway obstruction; Infant

Obliterative lower airway lesions in childhood: bronchoscopic diagnosis and clinical spectrum

Previous reports have described structural airway abnormalities in children with non-cystic fibrosis chronic supportive lung disease as well as obliterative membranes in the major bronchi of cystic fibrosis patients. The putative paradigm proposed in the evolution of these membranes invokes intense inflammation resulting in granulation tissue and neovascularization with the formation of pyogenic granuloma and eventually fibrosis. Our series of four cases widens the spectrum of conditions that may be conducive to large airway obliteration to include non-suppurative chronic infections and possibly immunosuppression. Obliteration of lumina in proximal and distal airways was visualized on bronchoscopy, the latter by the use of the ultrathin bronchoscopes. An attempt at invasive intervention by transbronchial breaching of the obstruction was unsuccessful in three cases, and in one case, the obliterative process resolved spontaneously and without any radiologic trace, presumably by resorption or rupture or through development of collateral ventilation. This series highlights the use of bronchoscopy for diagnosis and occasionally for therapeutic intervention in hitherto little recognized obliterative airway lesions. These acquired obliterative lesions should be considered in the evaluation of patients with isolated non-resolving pulmonary infiltrates or other conditions in which bronchial and bronchiolar patency may be impaired. Pediatr Pulmonol. 2014; 49:E27–E34. © 2013 Wiley Periodicals, Inc.

Síndrome de microdeleción 22q11: manifestaciones cardiorrespiratorias y utilidad de la fibrobroncoscopia

The 22q11 deletion syndrome is a frequent contiguous-gene deletion syndrome. This disorder has a broad spectrum of phenotypic manifestations. It includes various syndromes such as DiGeorge syndrome.The most frequent clinical manifestations are congenital cardiac defects, characteristic facies, palate malformations, hypoparathyroidism, immunodeficiency due to thymic hypoplasia, growth retardation, and behavioural and psychiatric problems.Among the symptoms observed, many patients suffer from respiratory insufficiency or failure. The origin is often multifactorial. Structural airway abnormalities are frequently found in this syndrome. In many of these patients the malformation is mild or non-existent, and remains asymptomatic. However, in some cases it can cause a severe respiratory insufficiency, being diagnosed when other disorders are ruled out.These cases illustrate the importance of early visualisation of the airway by fibrobronchoscopy in the management of the patient with 22q11 deletion syndrome who has recurrent respiratory difficulties.