Lung Function In Young Children Research Articles

Associations between prenatal and early-life air pollution exposure and lung function in young children: Exploring influential windows of exposure on lung development

BackgroundEvidence in the literature suggests that air pollution exposures experienced prenatally and early in life can be detrimental to normal lung development, however the specific timing of critical windows during development is not fully understood. ObjectivesWe evaluated air pollution exposures during the prenatal and early-life period in association with lung function at ages 6–9, in an effort to identify potentially influential windows of exposure for lung development. MethodsOur study population consisted of 222 children aged 6–9 from the Fresno-Clovis metro area in California with spirometry data collected between May 2015 and May 2017. We used distributed-lag non-linear models to flexibly model the exposure-lag-response for monthly average exposure to fine particulate matter (PM2.5) and ozone (O3) during the prenatal months and first three years of life in association with forced vital capacity (FVC), and forced expiratory volume in the first second (FEV1), adjusted for covariates. ResultsPM2.5 exposure during the prenatal period and the first 3-years of life was associated with lower FVC and FEV1 assessed at ages 6–9. Specifically, an increase from the 5th percentile of the observed monthly average exposure (7.55 μg/m3) to the median observed exposure (12.69 μg/m3) for the duration of the window was associated with 0.42 L lower FVC (95% confidence interval (CI): −0.82, −0.03) and 0.38 L lower FEV1 (95% CI: −0.75, −0.02). The shape of the lag-response indicated that the second half of pregnancy may be a particularly influential window of exposure. Associations for ozone were not as strong and typically CIs included the null. ConclusionsOur findings indicate that prenatal and early-life exposures to PM2.5 are associated with decreased lung function later in childhood. Exposures during the latter months of pregnancy may be especially influential.

Associations between prenatal and early-life air pollution exposure and lung function in young children: exploring influential windows of exposure on lung development

Associations between prenatal and early-life air pollution exposure and lung function in young children: exploring influential windows of exposure on lung development

Associations between Prenatal and Early-Life Air Pollution Exposure and Lung Function in Young Children: Exploring Influential Windows of Exposure on Lung Development

Associations between Prenatal and Early-Life Air Pollution Exposure and Lung Function in Young Children: Exploring Influential Windows of Exposure on Lung Development

Impulse oscillometry and free-running tests for diagnosing asthma and monitoring lung function in young children

BackgroundSeparating individuals with viral-induced wheezing from those with asthma is challenging, and there are no guidelines for children under 6 years of age. Impulse oscillometry, however, is feasible in 4-year-old children. ObjectiveTo explore the use of impulse oscillometry in diagnosing and monitoring asthma in young children and evaluating treatment response to inhaled corticosteroid (ICS). MethodsA total of 42 children (median age 5.3 years, range 4.0-7.9 years) with physician-diagnosed asthma and lability in oscillometry were followed for 6 months after initiation of ICS treatment. All children performed the 6-minute free-running test and impulse oscillometry at 3 time points. After the baseline, they attended a second visit when they had achieved good asthma control and a third visit approximately 60 days after the second visit. A positive ICS response was defined as having greater than 19 points in asthma control test and no hyperreactivity on the third visit. ResultsIn total, 38 of 42 children responded to ICS treatment. Exercise-induced increases of resistance at 5 Hz decreased after ICS treatment (61% vs 18% vs 13.5%, P < .001), and running distance during the 6-minute test was lengthened (800 m vs 850 m vs 850 m, P = .001). Significant improvements in childhood asthma control scores occurred between the baseline and subsequent visits (21 vs 24 vs 24, P < .001) and acute physicians’ visits for respiratory symptoms (1, (0–6) vs 0, (0–2), P = .001). Similar profiles were observed in children without aeroallergen sensitization and among those under 5 years of age. ConclusionImpulse oscillometry is a useful tool in diagnosing asthma and monitoring lung function in young children.

Residential Greenness, Asthma, and Lung Function in Young Children

Background. While benefits of greenness to health have been reported, studies specific to child respiratory health are scarce and findings are inconsistent. Objective. Exposure to greenness and respiratory outcomes were examined among the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) cohort from birth to age 7 years. Methods. Residential surrounding greenness was averaged using the Normalized Difference Vegetation Index (NDVI) within 200, 400, and 800 meter distances from the home address at birth, age 7 years, and cumulative exposure across childhood (averaged for each year from birth to age 7 years). Respiratory outcomes were assessed at age 7 years, including lung function [percent predicted FEV1 (%FEV1), percent predicted FVC (%FVC), and percent predicted FEV1/FVC (%FEV1/FVC)] and asthma. The associations of a 0.1 unit increase in NDVI with respiratory outcomes were assessed using linear and logistic regression models adjusted for community deprivation, household income, and traffic-related air pollution. Results. Mean NDVI was significantly higher among children without asthma compared to those with asthma at birth in 200 meter and 800 meter distances from the home, and across childhood 200 meters from the home. No relationship was observed between NDVI at any age or buffer distance and asthma after adjustment. NDVI was significantly positively correlated with %FEV1 and %FVC for all distances at age 7 years and across childhood, and at 800 meters at birth. After adjustment, NDVI at age 7 years was significantly associated with %FEV1 (200 meters: β=2.05, 95% CI: [0.08, 3.3]; 400 meters: β=1.64, 95% CI: [0.3, 2.9]) and %FVC (200 meters: β=1.84, 95% CI: [0.7, 3.0]; 400 meters: β=1.55, 95% CI: [0.3, 2.8]; 800 meters: β=1.45, 95% CI: [0.1, 2.8]). No relationship was found between greenness and %FEV1/FVC. Conclusions. Greenness may not increase risk for child asthma, but may be beneficial to concurrent lung function.

Impulse Oscillometry to Evaluate Lung Function in Young Children Under Five Years with Sickle Cell Disease

BACKGROUND Young children with sickle cell disease (SCD) aged 2 - 5 years old are at the highest risk of acute chest syndrome (ACS), a leading cause of morbidity and mortality. In addition to severe forms of SCD (HbSS and HbSβ0 thalassemia), asthma and airway hyper-responsiveness are also known risk factors for ACS, and are three to five times more prevalent in older children and adults with SCD. However in SCD children under 5 years there are only a few studies describing airway function, due to limitations in spirometry and other common pulmonary function tests (PFTs). Impulse oscillometry, a passive, non-invasive technique to evaluate airway function via pulmonary resistance and reactance, has been validated in children as young as 3 years, but has not been used widely in children with SCD. OBJECTIVE We sought to describe baseline airway function in children under 5 years with SCD using impulse oscillometry, as part of an ongoing observational study to evaluate lung function in young SCD children over time. METHOD Following IRB approval, participation in the ongoing prospective study was offered to patients aged 3 - 5 years old with HbSS and HbSβ0 thalassemia followed at the Pediatric Sickle Cell Clinic at Augusta University. Parents of the consented patients completed a modified ISAAC questionnaire assessing reported asthma symptoms and tobacco smoke exposure. Baseline IOS was obtained within 6 months of consent, with other clinical data obtained from medical records. Airway function was assessed using airway resistance at 5Hz and 20Hz (R5, R20), and reactance at 5Hz (X5). Percent predicted values were computed using NHANES (National Health and Nutrition Examination Survey) reference criteria for age, height, gender and ethnicity. RESULTS Out of 9 consented patients, 7 completed the ISAAC questionnaire and 6 successfully performed IOS. One patient consented but deferred participation to next visit and 1 patient with HbSC was excluded from analysis. All remaining patients had sickle cell anemia (HbSS). Age range at study enrolment was 3.7 - 5.4 years (mean 4.6 years). All participants were African American, 4/7 were male. Four out of 7 survey participants were already on Hydroxyurea therapy for their disease with therapy duration ranging from 2 - 41 months. None had preceding history of ACS. One survey respondent reported asthma symptoms (wheezing, dry cough at night) in preceding 12 months and 1 reported passive tobacco exposure. None reported a prior asthma diagnosis. Of the 6 participants with PFT data, baseline percent-predicted values for IOS parameters R5 and R20 were 114.83 ± 22.37 and 97.83 ± 23.11 respectively. Baseline X5 (%pred) was 76.33 ± 48.59. DISCUSSION Our preliminary results show normal baseline airway function in this subset of young SCA patients, with R5 representing total airway resistance, and R20 representing resistance in large airways. Small airway function can be deduced from differences between R5 and R20. Airway resistance decreases with age, and early changes in small airway resistance can be seen in children with asthma and obstructive symptoms. Low frequency reactance serves as a measure of airway distensibility, especially in the distal airways. Therefore, conditions affecting lung elasticity would result in abnormal X5. Ongoing data collection and follow-up will help us study how airway function evolves in young children with SCA with or without underlying asthma. We will also assess the effects of Hydroxyurea and other disease-modifying therapies on airway function over time. Disclosures No relevant conflicts of interest to declare.

Prenatal exposure to perfluoroalkyl substances, immune-related outcomes, and lung function in children from a Spanish birth cohort study.

Prenatal exposure to perfluoroalkyl substances (PFASs) has been associated with impaired immune and respiratory health during childhood but the evidence is inconsistent and limited for lung function. We studied the association between prenatal PFASs exposure and immune and respiratory health, including lung function, up to age 7 years in the Spanish INMA birth cohort study. We assessed four PFASs in maternal plasma samples collected during the 1st trimester of pregnancy (years: 2003-2008): perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorononanoate (PFNA). Mothers reported the occurrence (yes/no) of lower respiratory tract infections, wheezing, asthma, and eczema in the previous 12 months at 1.5 and 4 years of the child (n = 1188) and at 7 years (n = 1071). At ages 4 (n = 503) and 7 (n = 992) years lung function was assessed using spirometry tests. The most abundant PFASs were PFOS and PFOA (geometric means: 5.80 and 2.31 ng/mL, respectively). The relative risk of asthma during childhood per each doubling in PFNA concentration was 0.74 (95 CI%: 0.57, 0.96). The relative risk of eczema during childhood per every doubling in PFOS concentration was 0.86 (95 CI%: 0.75, 0.98). Higher PFOA concentrations were associated with lower forced vital capacity and lower forced expiratory volume in 1 s z-scores at 4 years [β (95 CI %): -0.17 (-0.34, -0.01) and -0.13 (-0.29, 0.03), respectively], but not at 7 years. This longitudinal study suggests that different PFASs may affect the developing immune and respiratory systems differently. Prenatal exposure to PFNA and PFOS may be associated with reduced risk of respiratory and immune outcomes, particularly asthma and eczema whereas exposure to PFOA may be associated with reduced lung function in young children. These mixed results need to be replicated in follow-up studies at later ages.

Early life exposure to coal mine fire smoke emissions and altered lung function in young children.

Long-term respiratory risks following exposure to relatively short periods of poor air quality early in life are unknown. We aimed to evaluate the association between exposure to a 6-week episode of air pollution from a coal mine fire in children aged <2 years, and their lung function 3 years after the fire. We conducted a prospective cohort study. Individual exposure to 24-h average and peak concentrations of particulate matter with an aerodynamic diameter <2.5 μm in diameter (PM2.5 ) during the fire were estimated using dispersion and chemical transport modelling. Lung function was measured using the forced oscillation technique (FOT), generating standardized Z-scores for resistance and reactance at a frequency of 5 Hz (Rrs5 and Xrs5 ), and area under the reactance curve (AX). We used linear regression models to assess the associations between PM2.5 exposure and lung function, adjusted for potential confounders. Of the 203 infants originally recruited, 84 aged 4.3 ± 0.5 years completed FOT testing. Median (interquartile range, IQR) for average and peak PM2.5 were 7.9 (6.8-16.8) and 103.4 (60.6-150.7) μg/m3 , respectively. The mean ± SD Z-scores for Rrs5 , Xrs5 and AX were 0.56 ± 0.80, -0.76 ± 0.88 and 0.72 ± 0.92, respectively. After adjustment for potential confounders including maternal smoking during pregnancy, a 10 μg/m3 increase in average PM2.5 was significantly associated with worsening AX (β-coefficient: 0.260; 95% CI: 0.019, 0.502), while the association between a 100-μg/m3 increase in peak PM2.5 and AX was borderline (0.166; 95% CI: -0.002, 0.334). Infant exposure to coal mine fire emissions could be associated with long-term impairment of lung reactance.

Peak OGTT glucose is associated with lower lung function in young children with cystic fibrosis

BackgroundScreening for Cystic Fibrosis-related diabetes is recommended in patients with CF <10 years old when there are concerns about growth and lung function. The Oral Glucose Tolerance Test (OGTT) is recommended but has not been validated in this cohort. We sought to determine whether the 2-h OGTT, the gold standard diagnostic test for CFRD, detects clinical decline in children with CF <10 years old. MethodsWe analysed blood glucose(BG) levels collected every 30 min during OGTT in 27 children with CF < 10 years old, comparing the 2-hour BG (BG120min), peak BG (BGmax) and Area Under the Curve(AUC) for glucose and the association with lung function and nutritional status. We also compared the OGTT results with results from Continuous Glucose Monitoring (CGM) performed in 11 participants. ResultsThe BGmax was higher than the BG120min in 25/27 (93%) participants. There was a significant inverse correlation between BGmax and weight z-score (rs = −0.56, p = .002) and between BGmax and FEV1 (rs = −0.54, p = .014) that was not present for BG120min. A significant inverse correlation was also identified between fasting insulin level and elevated glucose on CGM, defined as AUC >7.8 mmol/L (rs = − 0.69, p = .027) or as % time > 7.8 (rs = − 0.76, p = .011). ConclusionsChildren with CF < 10 years of age with higher BGmax on OGTT have lower lung function and weight z- scores that may not be identified using the 2 h OGTT BG120min. CGM also identifies glucose excursions in young children with CF.

Small airway oscillometry indices: Repeatability and bronchodilator responsiveness in young children.

The impulse oscillometry (IOS) indices absolute and relative difference between respiratory resistance at 5 and 20 Hz (R5-20 and R5-20%, respectively) and the area under the reactance curve (AX) are postulated to reflect small airway function. Data on their cutoff values to evaluate bronchodilator responsiveness (BDR) or between-visit changes after interventions are limited in young children. We evaluated the BDR of 103 healthy children aged 2-7 years, who received either salbutamol (n = 84) or placebo (n = 19) in order to determine cutoff values for BDR of R5-20, R5-20%, and AX. We then determined the repeatability within and between two IOS measurements 7-14 days apart in young children aged 4-8 years with asthmatic symptoms (n = 43), including cutoff values for significant between-visit changes. The investigated IOS parameters showed marked BDR (fifth percentile cutoff of 75-110% of the baseline value) in healthy children, whereas no significant changes were seen after inhalation of placebo. The agreement within the triplicate IOS measurement was excellent (ICC > 0.80), and the agreement of results between visits was good (ICC > 0.60). A change in R5-20, R5-20%, and AX of 0.65, 1.08, and 0.84 z-scores, respectively, would exceed 95% confidence intervals for between-visit variability. We introduce cutoff values for BDR of R5-20, R5-20%, and AX, and their repeatability indices and cutoff limits for significant between-visit changes. These IOS parameters may show greater variability than the conventional IOS indices during follow-up, but the between-visit agreement remains good, providing potentially useful endpoints for monitoring lung function in young children.

Progressive ventilation inhomogeneity in infants with cystic fibrosis after pulmonary infection

Measures of ventilation distribution are promising for monitoring early lung disease in cystic fibrosis (CF). This study describes the cross-sectional and longitudinal impacts of pulmonary inflammation and infection on ventilation homogeneity in infants with CF.Infants diagnosed with CF underwent multiple breath washout (MBW) testing and bronchoalveolar lavage at three time points during the first 2 years of life.Measures were obtained for 108 infants on 156 occasions. Infants with a significant pulmonary infection at the time of MBW showed increases in lung clearance index (LCI) of 0.400 units (95% CI 0.150-0.648; p=0.002). The impact was long lasting, with previous pulmonary infection leading to increased ventilation inhomogeneity over time compared to those who remained free of infection (p<0.05). Infection with Haemophilus influenzae was particularly detrimental to the longitudinal lung function in young children with CF where LCI was increased by 1.069 units for each year of life (95% CI 0.484-1.612; p<0.001).Pulmonary infection during the first year of life is detrimental to later lung function. Therefore, strategies aimed at prevention, surveillance and eradication of pulmonary pathogens are paramount to preserve lung function in infants with CF.

Early respiratory infection is associated with reduced spirometry in children with cystic fibrosis.

Pulmonary inflammation, infection, and structural lung disease occur early in life in children with cystic fibrosis. We hypothesized that the presence of these markers of cystic fibrosis lung disease in the first 2 years of life would be associated with reduced lung function in childhood. Lung function (forced expiratory volume in the first three-quarters of a second [FEV0.75], FVC) was assessed in individuals with cystic fibrosis diagnosed after newborn screening and healthy subjects during infancy (0-2 yr) and again at early school age (4-8 yr). Individuals with cystic fibrosis underwent annual bronchoalveolar lavage fluid examination, and chest computed tomography. We examined which clinical outcomes (pulmonary inflammation, infection, structural lung disease, respiratory hospitalizations, antibiotic prophylaxis) measured in the first 2 years of life were associated with reduced lung function in infants and young children with cystic fibrosis, using a mixed effects model. Children with cystic fibrosis (n = 56) had 8.3% (95% confidence interval [CI], -15.9 to -6.6; P = 0.04) lower FEV0.75 compared with healthy subjects (n = 18). Detection of proinflammatory bacterial pathogens (Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Aspergillus species, Streptococcus pneumoniae) in bronchoalveolar lavage fluid was associated with clinically significant reductions in FEV0.75 (ranging between 11.3 and 15.6%). The onset of lung disease in infancy, specifically the occurrence of lower respiratory tract infection, is associated with low lung function in young children with cystic fibrosis. Deficits in lung function measured in infancy persist into childhood, emphasizing the need for targeted therapeutic interventions in infancy to maximize functional outcomes later in life.

Repeatability and bronchodilator reversibility of lung function in young children

Knowledge of short- and longer-term repeatability of lung function in health and disease is essential to determine bronchodilator reversibility thresholds and to recognise if changes in lung function represent disease progression, therapeutic intervention or normal variability. Multiple-breath washout indices (lung clearance index, conductive ventilation inhomogeneity (Scond)) and specific airway resistance (sRaw) were measured in healthy children and stable wheezers. Measurements were performed at baseline and after 20 min without intervention to assess repeatability and determine bronchodilator reversibility thresholds. Bronchodilator reversibility was assessed by repeating baseline measurements 20 min after inhaled salbutamol. 28 healthy controls, mean±sd age 6.1±0.7 years and 62 wheezers 5.4±0.6 years were tested. Baseline variability in multiple-breath washout indices and sRaw was not significantly different between wheezers and healthy controls. Significant bronchodilator reversibility was only observed in wheezers for Scond (16%), but in both wheezers (37%) and healthy controls (20%) for sRaw. Some wheezers and healthy controls demonstrated increases in multiple-breath washout indices post-bronchodilator. Lung clearance index and sRaw demonstrate low baseline variability in healthy and diseased subjects. Neither multiple-breath washout indices nor sRaw are ideal for assessing bronchodilator reversibility in young children with stable wheeze. These findings will help to interpret the effect of therapeutic interventions in children with respiratory diseases.

S32 Cyclical mechanical stretch enhances the pro-fibrotic responses of primary embryonic foetal fibroblasts, but not ADAM33 expression

RationaleA Disintegrin And Metalloprotease (ADAM)33 is a susceptibility gene associated with asthma, bronchial hyperresponsiveness (BHR) and reduced lung function in young children. It is selectively expressed in mesenchymal cells, including...

Lung function in children with repaired tracheo‐oesophageal fistula using the forced oscillation technique

Tracheo-oesophageal fistula (TOF) and oesophageal atresia (OA) are congenital anomalies commonly associated with pulmonary complications during early childhood. This study investigated the role of the forced oscillation technique (FOT) in assessing lung function in young children with repaired TOF/OA. Forty children with repaired TOF/OA of median (range) age 8.0 (3.3-10.6) years, and 20 healthy children without TOF aged 6.1 (3.1-10.8) years were studied. FOT measurements were attempted in all subjects and spirometry only in those 6 years and above. Resistance and reactance (both hPasL(-1)) at 6 Hz (Rrs6 and Xrs6, respectively) and 8 Hz (Rrs8 and Xrs8) measured using FOT, and forced expired volume in 1 sec (FEV(1)), forced vital capacity, functional residual capacity, total lung capacity, and residual volume (all L) obtained from spirometry or plethysmography were compared with reference values and expressed as z-scores. Technically acceptable measurements of Rrs6, Rrs8, Xrs6, Xrs8, Fdep, and Fres were obtained in 37 children with TOF and 20 healthy children without TOF, respectively. Those with TOF had significantly higher mean (SD) z-scores for Rrs6 [0.99 (0.75)] versus healthy children without TOF [0.31 (0.69)] and lower mean (SD) z-scores for Xrs6 [-1.04 (1.07)] versus healthy children without TOF [-0.34 (0.83)]. Spirometry was successful in 24 of the 29 with TOF in whom it was attempted and all healthy children without TOF. Mean (SD) z-score for FEV(1) was significantly lower in those with TOF [-0.86 (1.13)] versus healthy children without TOF [0.67 (0.54)]. z-Scores for Rrs6 and FEV(1) were significantly correlated (r = -0.49; P = 0.003). Children with repaired TOF have diminished lung function compared with healthy children. FOT is sensitive and correlates well with standard spirometry. It can be used to measure lung function in younger children when spirometry is difficult to perform and should be considered as an objective method for monitoring clinical progress in young children with TOF.

Clinical findings associated with abnormal lung function in children aged 3–26 months with recurrent respiratory symptoms

To evaluate whether there are any associations between parentally reported symptoms, clinical findings and lung function in young children with recurrent lower respiratory tract symptoms. In 2000-2003, 148 children, aged 3-26 months, with recurrent lower respiratory tract symptoms underwent physical examination, investigation of a chest radiograph, whole body plethysmography and skin prick testing to common food and inhalant allergens. Lung function was considered abnormal (i.e. functional residual capacity z-score of > or =1.65 and/or specific conductance z-score of < or =-1.65) in 83 (56%) children. Findings of increased work of breathing (p < 0.001) and nonspecific noisy breathing sounds (p < 0.001) in the physical examination, as well as an abnormal chest radiograph (p = 0.028) were independently associated with abnormal lung function, explaining up to 34% of the variation in lung function. In contrast, parentally reported respiratory symptoms, environmental exposures or atopic trait were not associated with lung function abnormalities. The results of this study emphasize the importance of the meticulous clinical examination in the evaluation of early childhood respiratory disorders. As physical examination alone cannot predict lung function abnormalities reliably in preschool children with troublesome respiratory symptoms, lung function testing may be considered in such patients to obtain additional objective information.

Body composition and lung function in young children with cystic fibrosis

Body composition and lung function in young children with cystic fibrosis

Lipidomics of cellular and secreted phospholipids from differentiated human fetal type II alveolar epithelial cells

Maturation of fetal alveolar type II epithelial cells in utero is characterized by specific changes to lung surfactant phospholipids. Here, we quantified the effects of hormonal differentiation in vitro on the molecular specificity of cellular and secreted phospholipids from human fetal type II epithelial cells using electrospray ionization mass spectrometry. Differentiation, assessed by morphology and changes in gene expression, was accompanied by restricted and specific modifications to cell phospholipids, principally enrichments of shorter chain species of phosphatidylcholine (PC) and phosphatidylinositol, that were not observed in fetal lung fibroblasts. Treatment of differentiated epithelial cells with secretagogues stimulated the secretion of functional surfactant-containing surfactant proteins B and C (SP-B and SP-C). Secreted material was further enriched in this same set of phospholipid species but was characterized by increased contents of short-chain monounsaturated and disaturated species other than dipalmitoyl PC (PC16:0/16:0), principally palmitoylmyristoyl PC (PC16:0/14:0) and palmitoylpalmitoleoyl PC (PC16:0/16:1). Mixtures of these PC molecular species, phosphatidylglycerol, and SP-B and SP-C were functionally active and rapidly generated low surface tension on compression in a pulsating bubble surfactometer. These results suggest that hormonally differentiated human fetal type II cells do not select the molecular composition of surfactant phospholipid on the basis of saturation but, more likely, on the basis of acyl chain length.

N4/228 – Development of reliable prediction equations for lung function in young children

N4/228 – Development of reliable prediction equations for lung function in young children

*Lung Function in Young Children with Recurrent Wheeze and Cough: Relationship to Bronchoscopic and Bronchoalveolar Lavage Fluid (BALF) Findings.

*Lung Function in Young Children with Recurrent Wheeze and Cough: Relationship to Bronchoscopic and Bronchoalveolar Lavage Fluid (BALF) Findings.