Background It is increasingly evident that microbial colonization of the respiratory tract might have a role in the pathogenesis of asthma. Objective We sought to characterize and compare the ...microbiome of induced sputum in asthmatic and nonasthmatic adults. Methods Induced sputum samples were obtained from 10 nonasthmatic subjects and 10 patients with mild active asthma (8/10 were not using inhaled corticosteroids). Total DNA was extracted from sputum supernatants and amplified by using primers specific for the V6 hypervariable region of bacterial 16s rRNA. Samples were barcoded, and equimolar concentrations of 20 samples were pooled and sequenced with the 454 GS FLX sequencer. Sequences were assigned to bacterial taxa by comparing them with 16s rRNA sequences in the Ribosomal Database Project. Results All sputum samples contained 5 major bacterial phyla: Firmicutes, Proteobacteria, Actinobacteria, Fusobacterium, and Bacteroidetes, with the first 3 phyla accounting for more than 90% of the total sequences. Proteobacteria were present in higher proportions in asthmatic patients (37% vs 15%, P < .001). In contrast, Firmicutes (47% vs 63%, P = .17) and Actinobacteria (10% vs 14%, P = .36) were found more frequently in samples from nonasthmatic subjects, although this was not statistically significant. Hierarchical clustering produced 2 significant clusters: one contained primarily asthmatic samples and the second contained primarily nonasthmatic samples. In addition, samples from asthmatic patients had greater bacterial diversity compared with samples from nonasthmatic subjects. Conclusion Patients with mild asthma have an altered microbial composition in the respiratory tract that is similar to that observed in patients with more severe asthma.
Summary Background Together with smoking, the lung function attained in early adulthood is one of the strongest predictors of chronic obstructive pulmonary disease. We aimed to investigate whether ...lung function in early adulthood is, in turn, affected by airway function measured shortly after birth. Methods Non-selected infants were enrolled at birth in the Tucson Children's Respiratory Study between 1980 and 1984. We measured maximal expiratory flows at functional residual capacity (VmaxFRC ) in 169 of these infants by the chest compression technique at a mean of 2·3 months (SD 1·9). We also obtained measurements of lung function for 123 of these participants at least once at ages 11, 16, and 22 years. Indices were forced expiratory volume in 1 s (FEV1 ), forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of FVC (FEF25–75 ), both before and after treatment with a bronchodilator (180 μg of albuterol). Findings Participants who had infant VmaxFRC in the lowest quartile also had lower values for the FEV1 /FVC ratio (−5·2%, p<0·0001), FEF25–75 (−663 mL/s, p<0·0001), and FEV1 (−233 mL, p=0·001) up to age 22, after adjustment for height, weight, age, and sex, than those in the upper three quartiles combined. The magnitude and significance of this effect did not change after additional adjustment for wheeze, smoking, atopy, or parental asthma. Interpretation Poor airway function shortly after birth should be recognised as a risk factor for airflow obstruction in young adults. Prevention of chronic obstructive pulmonary disease might need to start in fetal life.
Summary Background Incidence of asthma increases during early adulthood. We aimed to estimate the contributions of sex and early life factors to asthma diagnosed in young adults. Methods 1246 healthy ...newborn babies were enrolled in the Tucson Children's Respiratory Study. Parental characteristics, early-life wheezing phenotypes, airway function, and bronchial hyper-responsiveness to cold dry air and sensitisation to Alternaria alternata were determined before age 6 years. Physician-diagnosed asthma, both chronic and newly diagnosed, and airway function were recorded at age 22 years. Findings Of 1246 babies enrolled, 849 had follow-up data at 22 years. Average incidence of asthma at age 16–22 years was 12·6 per thousand person-years. 49 (27%) of all 181 cases of active asthma at 22 years were newly diagnosed, of which 35 (71%) were women. Asthma remittance by 22 years was higher in men than in women (multinomial odds ratio M-OR 2·0, 95% CI 1·2–3·2, p=0·008). Age at diagnosis was linearly associated with the ratio of forced expiratory volume at 1 s to forced vital capacity at age 22 years. Factors independently associated with chronic asthma at 22 years included onset at 6 years (7·4, 3·9–14·0) and persistent wheezing (14·0, 6·8–28·0) in early life, sensitisation to A alternata (3·6, 2·1–6·4), low airway function at age 6 years (2·1, 1·1–3·9), and bronchial hyper-responsiveness at 6 years (4·5, 1·9–10·0). Bronchial hyper-responsiveness (6·9, 2·3–21·0), low airway function at 6 years (2·8, 1·1–6·9), and late-onset (4·6, 1·7–12·0) and persistent wheezing (4·0, 1·2–14·0) predicted newly diagnosed asthma at age 22 years. Interpretation Asthma with onset in early adulthood has its origins in early childhood. Funding National Heart Lung and Blood Institute.
Diminished lung function and increased prevalence of asthma have been reported in children with a history of early lower respiratory illnesses (LRIs), including pneumonia. Whether these associations ...persist up to adulthood has not been established.
As part of the prospective Tucson Children's Respiratory Study, LRIs during the first 3 years of life were ascertained by pediatricians. Spirometry was performed at ages 11, 16, 22, and 26 years. The occurrence of asthma/wheeze during the previous year was ascertained at ages 11, 13, 16, 18, 22, 24, 26, and 29 years. Longitudinal random effects models and generalized estimating equations were used to assess the relation of LRIs to lung function and asthma.
Compared with participants without early-life LRIs, those with pneumonia had the most severe subsequent lung function impairment, with mean ± SE deficits of -3.9% ± 0.9% (P < .001) and -2.5% ± 0.8% (P = .001) for pre- and post-bronchodilator FEV1:FVC ratio from age 11 to 26 years, respectively. Pneumonia was associated with increased risk for asthma (odds ratio OR: 1.95; 95% confidence interval CI: 1.11-3.44) and wheeze (OR: 1.94; 95% CI: 1.28-2.95) over the same age range. Early non-pneumonia LRIs were associated with mildly impaired pre-bronchodilator FEV1 (-62.8 ± 27.9 mL, P = .024) and FEV1:FVC ratio (-1.1 ± 0.5%, P = .018), and wheeze (OR: 1.37; 95% CI: 1.09-1.72).
Early pneumonia is associated with asthma and impaired airway function, which is partially reversible with bronchodilators and persists into adulthood. Early pneumonia may be a major risk factor for adult chronic obstructive pulmonary disease.
Low maximally attained lung function increases the risk of chronic obstructive pulmonary disease irrespective of the subsequent rate of lung function decline.
We aimed to determine if there were ...individuals with a distinct, persistently low lung function trajectory in the CRS (Tucson Children's Respiratory Study).
The CRS, an ongoing birth cohort study, enrolled 1,246 participants between 1980 and 1984. Latent class linear mixed effects modeling of the ratio of FEV1 to FVC was used to identify distinct lung function trajectories among participants with two or more spirometry measurements between ages 11 and 32 years.
Among 599 participants with 2,142 observations, a model with two distinct trajectories (a low trajectory n = 56; 9.3% and a normal trajectory) fit the data significantly better than a model with only one trajectory (P = 0.0007). As compared with those with a normal trajectory, participants with a persistently low trajectory were more likely to have a history of maternal asthma (20.0% vs. 9.9%; P = 0.02); early life lower respiratory illness caused by respiratory syncytial virus (41.2% vs. 21.4%; P = 0.001); and physician-diagnosed active asthma at age 32 years (43.9% vs. 16.2%; P < 0.001). Individuals with a persistently low trajectory also demonstrated lower lung function as measured by average maximal expiratory flow at functional residual capacity during infancy and at age 6 years.
A distinct group of individuals in a nonselected population demonstrates a persistently low lung function trajectory that may be partly established at birth and predisposes them to chronic obstructive pulmonary disease later in life.
Purpose The impact of the original International Children's Continence Society terminology document on lower urinary tract function resulted in the global establishment of uniformity and clarity in ...the characterization of lower urinary tract function and dysfunction in children across multiple health care disciplines. The present document serves as a stand-alone terminology update reflecting refinement and current advancement of knowledge on pediatric lower urinary tract function. Materials and Methods A variety of worldwide experts from multiple disciplines in the ICCS leadership who care for children with lower urinary tract dysfunction were assembled as part of the standardization committee. A critical review of the previous ICCS terminology document and the current literature was performed. In addition, contributions and feedback from the multidisciplinary ICCS membership were solicited. Results Following a review of the literature during the last 7 years the ICCS experts assembled a new terminology document reflecting the current understanding of bladder function and lower urinary tract dysfunction in children using resources from the literature review, expert opinion and ICCS member feedback. Conclusions The present ICCS terminology document provides a current and consensus update to the evolving terminology and understanding of lower urinary tract function in children. For the complete document visit http://jurology.com/.
Abstract Both non-invasive and invasive electroneurostimulation (ENS) modalities for bladder bowel dysfunction have been studied and reported in children. A summary of the proposed mechanism of ...actions and the more commonly used and recently reported techniques and outcomes are described. This includes transcutaneous electrical nerve stimulation, functional electrical nerve stimulation, intravesical electrical nerve stimulation, percutaneous tibial nerve stimulation and sacral neuromodulation in conditions including overactive bladder, enuresis, dysfunctional voiding, constipation, combined bladder bowel dysfunction and neuropathic bladder and bowel dysfunction. There is a need for further high quality randomised trials as well as long-term outcomes to establish whether ENS is able to alter the long-term trajectory for an individual child with bladder bowel dysfunction.
Background The association between vitamin D status at birth and childhood allergic outcomes is uncertain. The desert climate of Tucson offers a unique setting for studying the health effects of ...higher exposure to vitamin D. Objective To assess the relationship between cord blood 25-hydroxyvitamin D (25OHD) levels and allergic outcomes through age 5 years. Methods Cord blood 25(OH)D levels were measured in 219 participants in the Tucson Infant Immune Study, a population-based birth cohort. Plasma total IgE and specific IgE levels to 6 aeroallergens were measured at 1, 2, 3, and 5 years. Skin prick test (SPT) positivity (wheal diameter ≥3 mm) and physician-diagnosed active allergic rhinitis and asthma were assessed at age 5 years. Longitudinal models were used to assess the relationship between 25(OH)D and IgE levels. Logistic regression models were used to assess the relationship of 25(OH)D level with SPT positivity, allergic rhinitis, and asthma. Results The median cord blood 25(OH)D level was 64 nmol/L (interquartile range, 49-81 nmol/L). Relative to the reference group (50-74.9 nmol/L), both low (<50 nmol/L) and high (≥100 nmol/L) levels were associated with increased total IgE (coefficient = 0.27, P = .006 and coefficient = 0.27, P = .04, respectively) and detectable inhalant allergen-specific IgE (odds ratio = 2.4, P = .03 and odds ratio = 4.0, P = .01, respectively) through age 5 years. High 25(OH)D levels were also associated with increased SPT positivity (odds ratio = 4.0, P = .02). By contrast, the 25(OH)D level was not significantly associated with allergic rhinitis or asthma. Conclusion Both low and high levels of cord blood 25(OH)D were associated with increased aeroallergen sensitization. The association between vitamin D status and actual allergic diseases merits further study.
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