Lung Function Deficits Research Articles

Early smoke exposure is associated with asthma and lung function deficits in adolescents

ABSTRACTObjective: Early life tobacco smoke exposure may influence asthma, lung function and lung function growth into adolescence. We aimed to determine the associations between perinatal smoke exposure and asthma and lung function up to 18 years of age. Methods: We prospectively recorded perinatal parental smoking and measured respiratory outcomes at 12 and 18 years in the Melbourne Atopy Cohort Study (MACS), a longitudinal birth cohort. Multiple logistic regression was used to analyse the associations between perinatal smoke exposure and asthma at 12 (n = 370) and 18 years (n = 411). Multiple linear regression was used to investigate the relationship between perinatal smoking and: lung function (12 and 18 years) and lung function growth (between 12 and 18 years). Results: At 18 years, girls exposed to parental smoking during the perinatal period had increased odds of asthma (OR: 3.45, 95%CI: 1.36, 8.77), reduced pre-bronchodilator Forced expiratory volume in one-second (FEV1) (−272 ml/s; −438, −107); FEV1/ forced vital capacity (FVC) (−0.038; −0.065, −0.010); mid expiratory flow (MEF25-75) (−430 ml/s; −798, −61), and reduced post-bronchodilator FEV1/FVC (−0.028, −0.053, −0.004). No associations were found for boys (pre-bronchodilator FEV1 26ml/s; −202, 255; FEV1/FVC 0.018; −0.013, 0.049). Conclusions: Perinatal smoke may affect risk of asthma, reduce lung function and lung function growth in adolescence. Girls appear to be more susceptible than boys.

Sensitivity of newly defined impulse oscillometry indices in preschool children.

Early origins of chronic obstructive pulmonary disease have been recognized. Impulse oscillometry (IOS) is suitable for assessment of lung function also in preschool children, and some novel indices have been connected to assessment of small airway function. However, limited data exist on the sensitivity of these new indices to detect lung function deficits in young symptomatic children. IOS measurements of 103 healthy preschool children were evaluated to establish reference equations for the difference between respiratory resistance at 5 and 20 Hz (R5-20), the relative difference of R5-20 (R5-20%), and area under the reactance curve (AX). Thereafter, IOS results of children with late-onset troublesome lung symptoms (n = 20), a history of early wheeze (n = 37), or a history of bronchopulmonary dysplasia (BPD, n = 8) were compared to healthy children. None of the patient groups differed from healthy regarding respiratory resistance at 5 Hz (R5), and only children with a history of BPD differed from healthy regarding respiratory reactance at 5 Hz (X5). In contrast, z-scores of R5-20, R5-20%, and AX were significantly higher in all patient groups than in healthy children (P < 0.001), showing improved sensitivity (20-55%) compared to R5 and X5 (5-6%). R5-20, R5-20%, and AX are superior to conventional IOS parameters in distinguishing children with current or past lower respiratory tract symptoms from healthy, and may prove valuable for screening early lung function deficits. Pediatr Pulmonol. 2017;52:598-605. © 2016 Wiley Periodicals, Inc.

Body composition, lung function, and prevalent and progressive bone deficits among adults with cystic fibrosis

IntroductionCystic fibrosis (CF) is associated with osteoporosis and incident fracture. This study assessed independent predictors of baseline and 2-year changes in bone mineral density (BMD) in adults with CF. MethodsSixty-four adult patients with CF, ages 18–57, were recruited from the Massachusetts General Hospital Cystic Fibrosis Care Center. Dual-energy X-ray absorptiometry (DXA) was performed at the spine and radius at baseline and 2 years (in 39 subjects). Estimates of fat-free mass index (FFMI) and fat mass index (FMI) were determined using height, weight, and tetrapolar bioelectric impedance analysis. All subjects completed lung spirometry within 1 month of the study visit. Linear regression models evaluated predictors of baseline BMD Z-scores and change in PA spine BMD Z-score over 2 years. Two definitions of low BMD were studied based on Z-score (≤–1.0 and ≤–2.0). ResultsLow BMD was present in 52% of subjects. Subjects with low BMD were more likely to be male (67% vs. 32%, P=0.009), were more likely to be currently using glucocorticoids (21% vs. 0%, P<0.001), had lower percent body fat (P=0.04), and were more likely to have had a previous fracture (60% vs. 46%, P=0.007). In multivariable models, greater FFMI and height, but not greater FMI, were associated with greater BMD. In multivariable models, low forced vital capacity (FVC) and greater FMI were associated with greater loss of BMD at the PA spine over two years. ConclusionsMale sex, short stature, and low lean mass are associated with low BMD in CF. Greater adiposity and lower lung function are predictors of negative change in BMD Z-score over 2 years.

Childhood Wheeze Phenotypes Show Less Than Expected Growth in FEV1 Across Adolescence

Several “wheeze phenotypes” have been described in early childhood based on age of onset and persistence of wheezing. These include never/infrequent wheeze, early transient wheeze (begins in the first 12 months and resolves by age 3 years), early persistent wheeze (begins in the first 6 months), intermediate-onset wheeze (begins at around 18 months), and late-onset wheeze (begins after age 4 years). What becomes of these children’s lung function over time?An Australian prospective birth cohort of 620 high-allergy-risk children (at least 1 first-degree family member with a history of eczema, asthma, allergic rhinitis, severe food allergy, or any combination of these).Respiratory symptoms and spirometry were recorded at 12 and 18 years. Relationships were assessed comparing wheeze phenotypes and lung function.Deficits in expected growth of lung function, measured by change in forced expiratory volume in 1 second (FEV1) between 12 and 18 years, were found for early persistent (reduced 290 mL; 95% confidence interval [CI], 82–498), intermediate-onset (reduced 210 mL; 95% CI, 62–359), and late-onset wheeze (reduced 255 mL; 95% CI, 69–442). Current asthma risk was increased for all phenotypes except early transient, which was also not associated with lung function deficits at 12 or 18 years.This is the first study to show that persistent childhood wheeze phenotypes were associated with deficits in the growth of FEV1 through to late adolescence. In contrast, early transient wheeze was found to be a benign disorder for adolescent respiratory health.It is troubling that young children with persistent wheeze show marked reduction in lung function/growth as adolescents. This clearly emphasizes the importance of serial spirometry to identify children with declining lung function in whom more aggressive management of their asthma may prevent this. Although it is reassuring that those with early transient wheeze do not show such a decline in lung function, other studies have shown a significant rate of relapse of asthma in adults who had “outgrown” their childhood disease.

Long-term effects of pneumonia in young children.

Each year an estimated 120 million episodes of pneumonia occur in children younger than 5 years of age, resulting in one million deaths globally. Within this age group the lungs are still developing by increasing alveoli numbers and airway dimensions. Pneumonia during this critical developmental period may therefore adversely affect the lung’s structure and function, with increased risk of subsequent chronic lung disease. However, there are few longitudinal studies of pneumonia in otherwise healthy children that extend into adulthood to help address this important question. Birth cohort, longitudinal, case-control and retrospective studies have reported restrictive and obstructive lung function deficits, asthma, bronchiectasis, and chronic obstructive pulmonary disease. In particular, severe hospitalised pneumonia had the greatest risk for long-term sequelae. Most studies, however, were limited by incomplete follow-up, some reliance upon parental recall, risk of diagnostic misclassification, and potential confounders such as nutrition, social deprivation, and pre-existing small airways or lungs. More long-term studies measuring lung function shortly after birth are needed to help disentangle the complex relationships between pneumonia and later chronic lung disease, while also addressing host responses, types of infection, and potential confounding variables. Meanwhile, parents of young children with pneumonia need to be advised about the importance of symptom resolution, post-pneumonia. In addition, paying attention to factors associated with optimising lung growth such as good nutrition, minimising exposure to air pollution, avoiding cigarette smoke, and decreasing the risk of preventable infections through good hygiene and having their children fully vaccinated should be emphasised. Finally, in the developing world and for disadvantaged communities in developed countries, public health policies leading to good quality housing and heating, hygiene, education, and improving socio-economic status are also essential.

IL-10 Gene Polymorphisms Are Associated with Post-Bronchiolitis Lung Function Abnormalities at Six Years of Age.

AimInterleukin-10 (IL-10) has been associated with wheezing and asthma in children and the genetic variation of the IL-10 cytokine production may be linked to post-bronchiolitis lung function. We used impulse oscillometry (IOS) to evaluate the associations of IL10 polymorphisms with lung function at a median age of 6.3 years in children hospitalised for bronchiolitis before six months of age.MethodsWe performed baseline and post-exercise IOS on 103 former bronchiolitis patients. Data on single nucleotide polymorphisms (SNP) of IL10 rs1800896 (–1082G/A), rs1800871 (–819C/T), rs1800872 (–592C/A) were available for 99 children and of IL10 rs1800890 (–3575T/A) for 98 children.Results IL10 rs1800896, rs1800871 and rs1800872 combined genotype AA+CT+CA and carriage of haplotype ATA, respectively, were associated with higher resistance and lower reactance in baseline IOS in adjusted analyses. At IL10 rs1800890, the A/A-genotype and carriers of A-allele were associated with lower reactance in baseline IOS. There were no significant associations between the studied SNPs and airway hyper-reactivity to exercise.ConclusionLow-IL-10-producing polymorphisms in the IL-10 encoding gene were associated with obstructive lung function parameters, suggesting an important role for IL-10 in development of lung function deficit in early bronchiolitis patients.

Relation between circulating CC16 concentrations, lung function, and development of chronic obstructive pulmonary disease across the lifespan: a prospective study

Low concentrations of the anti-inflammatory protein CC16 (approved symbol SCGB1A1) in serum have been associated with accelerated decline in forced expiratory volume in 1 s (FEV1) in patients with chronic obstructive pulmonary disease (COPD). We investigated whether low circulating CC16 concentrations precede lung function deficits and incidence of COPD in the general population. We assessed longitudinal data on CC16 concentrations in serum and associations with decline in FEV1 and incidence of airflow limitation for adults who were free from COPD at baseline in the population-based Tucson Epidemiological Study of Airway Obstructive Disease ([TESAOD] n=960, mean follow-up 14 years), European Community Respiratory Health Survey ([ECRHS-Sp] n=514, 11 years), and Swiss Cohort Study on Air Pollution and Lung Diseases in Adults ([SAPALDIA] n=167, 8 years) studies. Additionally, we measured circulating CC16 concentrations in samples from children aged 4-6 years in the Tucson Children's Respiratory Study (n=427), UK Manchester Asthma and Allergy Study (n=481), and the Swedish Barn/children, Allergy, Milieu, Stockholm, Epidemiological survey (n=231) birth cohorts to assess whether low CC16 concentrations in childhood were predictive for subsequent lung function. After adjustment for sex, age, height, smoking status and intensity, pack-years, asthma, and FEV1 at baseline, we found an inverse association between CC16 concentration and decline in FEV1 in adults in TESAOD (4·4 mL/year additional FEV1 decline for each SD decrease in baseline CC16 concentration, p=0·0014) and ECRHS-Sp (2·4 mL/year, p=0·023); the effect in SAPALDIA was marginal (4·5 mL/year, p=0·052). Low CC16 concentration at baseline was also associated with increased risk of incident stage 2 airflow limitation (ratio of FEV1 to forced expiratory volume [FEV1/FVC] less than 70% plus FEV1 % predicted less than 80%) in TESAOD and ECRHS-Sp. In children, the lowest tertile of CC16 concentrations was associated with a subsequent FEV1 deficit of 68 mL up to age 16 years (p=0·0001), which was confirmed in children who had never smoked by age 16 years (-71 mL, p<0·0001). Low concentrations of CC16 in serum are associated with reduced lung function in childhood, accelerated lung function decline in adulthood, and development of moderate airflow limitation in the general adult population. National Heart, Lung, and Blood Institute and European Union Seventh Framework Programme.

Ceramics manufacturing contributes to ambient silica air pollution and burden of lung disease.

Inhalation of silica (SiO2) in occupational exposures can cause pulmonary fibrosis (silicosis), lung function deficits, pulmonary inflammation, and lung cancer. Current risk assessment models, however, cannot fully explain the magnitude of silica-induced pulmonary disease risk. The purpose of this study was to assess human health risk exposed to airborne silica dust in Taiwan ceramics manufacturing. We conducted measurements to characterize workplace-specific airborne silica dust in tile and commodity ceramic factories and used physiologically based alveolar exposure model to estimate exposure dose. We constructed dose-response models for describing relationships between exposure dose and inflammatory responses, by which health risks among workers can be assessed. We found that silica contents were 0.22-33.04 % with mean concentration ranges of 0.11-5.48 and 0.46-1763.30 μg m(-3), respectively, in commodity and tile ceramic factories. We showed that granulation workers in tile ceramic factory had the highest total SiO2 lung burden (∼1000 mg) with cumulative SiO2 lung burden of ∼4 × 10(4) mg-year. The threshold estimates with an effect on human lung inflammation and fibrosis are 407.31 ± 277.10 (mean ± sd) and 505.91 ± 231.69 mg, respectively. For granulation workers, long-term exposure to airborne silica dust for 30-45 years was likely to pose severe adverse health risks of inflammation and fibrosis. We provide integrated assessment algorithms required to implement the analyses and maintain resulting concentration of silica dust at safety threshold level in the hope that they will stimulate further analyses and interpretation. We suggest that decision-makers take action to implement platforms for effective risk management to prevent the related long-term occupational disease in ceramics manufacturing.

Decreased FEV1 % in asthmatic adults in Scottish homes with high Environmental Relative Moldiness Index values.

SummaryBackgroundExposures to indoor biological contaminants have been implicated in asthma's aetiology but their effect on lung function is not well quantified.ObjectiveThe aim of this cross‐sectional study of non‐smoking, asthmatic adults in Scotland was to determine the correlation between the results from a standard spirometry test, forced expiratory volume in one‐second percent (FEV 1%), and quantitative estimates of some biological exposures.MethodsA population (n = 55) of non‐smoking, adult asthmatics in Scotland was included in this study and each completed a questionnaire that allowed the determination of the Asthma Control Questionnaire scores (ACQ) and St. George's Respiratory Questionnaire scores (SGRQ), as well as corticosteroid use. Spirometry testing was completed and the pre‐bronchodilator FEV 1% value calculated. At about the same time, floor dust samples were collected in the living room and in the bedroom. These dust samples were analysed for mould contamination, as described by the Environmental Relative Moldiness Index (ERMI) values and by (1, 3)‐β‐D‐glucan concentrations, for endotoxin, and for dust mite, cat, and dog allergen concentrations. The asthmatics' FEV 1% values were tested for correlation (Pearson) to questionnaire‐based estimates of health. Also, each biological exposure was tested for correlation (Pearson) to the FEV 1% values.Results FEV 1% results were correlated with ACQ scores (ρ −0.586, P < 0.001), SGRQ scores (ρ −0.313, P = 0.020), and weakly with corticosteroid use (ρ −0.221, P = 0.105). The ERMI values in the homes (average 5.3) were significantly correlated with FEV 1% values (ρ −0.378, P = 0.004). There was no correlation between FEV 1% and concentrations of endotoxin, (1, 3)‐β‐D‐glucan, or any of the allergens.Conclusion and clinical relevanceAlthough these results do not prove that mould exposures caused the deficit in lung function observed in this study, it might be advisable for asthmatics to avoid high ERMI environments.

Childhood asthma and chronic obstructive pulmonary disease: outcomes until the age of 50.

There has been recent interest in understanding the origins of chronic obstructive pulmonary disease. Epidemiological studies suggest that chronic obstructive pulmonary disease clearly has other causes apart from tobacco smoke. Cross-sectional studies of adult cohorts with chronic obstructive pulmonary disease highlight that childhood asthma is a risk factor. A recent longitudinal childhood cohort study of children from childhood to the age of 50 years describes that children with severe asthma are at increased risk of chronic obstructive pulmonary disease and that the deficit in lung function can be tracked back to early years. Children with severe asthma are at increased risk of developing chronic obstructive pulmonary disease.

Preschool oscillometry and lung function at adolescence in asthmatic children.

Reduced lung function in early childhood is associated with persistent symptoms and low lung function later in life. Impulse oscillometry (IOS) is feasible for assessing lung function also in preschool children, and some of the parameters, such as respiratory resistance at 5 Hz (Rrs5) and the frequency dependence of resistance (dRrs/df), have been suggested to reflect small airway dysfunction. Whether changes in preschool IOS predict later lung function remains unknown. The medical data of 154 asthmatic children with IOS performed at 2-7 years and spirometry at 12-18 years were analyzed. IOS and post-bronchodilator spirometry parameters were compared, and the association was estimated in a multivariate model. Measured at preschool age, particularly Rrs5 and dRrs/df were significantly correlated with post-bronchodilator forced expiratory volume in 1 sec (FEV1) at adolescence (Rrs5: r = -0.223, P = 0.005; dRrs/df: r = 0.234, P = 0.004). Although the number of children with decreased FEV1 was low, associations of increased Rrs5 (odds ratio (OR) 5.9, 95% confidence interval (CI) 1.7; 20.9) and decreased dRrs/df (OR 8.2, 95% CI 1.7; 39.6) with decreased FEV1 remained significant in multivariate analyses. Similar findings were observed also with other spirometric parameters. In asthmatic children, preschool IOS is associated with spirometric lung function at adolescence, but the scatter is wide. Normal preschool IOS seems to indicate favourable lung function outcome, whereas in some individuals IOS could potentially be of clinical use, at a younger age than spirometry, to screen lung function deficits and increased risk for later lung function impairment.

The association of normal range glycated hemoglobin with restrictive lung pattern in the general population.

Glycated hemoglobin (HbA1c) is an important diagnostic indicator of diabetes mellitus, and some authors have argued that it is related to impaired lung function in the diabetic population. However, there was rare study for association between lung function and HbA1c in the non-diabetic population. We investigated whether HbA1c below the diagnostic threshold is related to deficits in lung function. We analyzed biochemical and spirometry data from a nation-wide, population-based, case-control study (the KNHANES IV and V). Eligible as cases were all native Koreans aged 40 years or more with no medical illness. A total of 3670 participants were divided into 4 groups according to HbA1c (%) as follows: Group I (n = 842), ≥ 4.0 and ≤ 5.3; Group II (n = 833), > 5.3 and ≤ 5.5; Group III (n = 898), > 5.5 and ≤ 5.7; and Group IV (n = 1097), > 5.7 and ≤ 6.4. Group I had the greatest forced vital capacity (FVC, 96.3 ± 0.5% pred, P < 0.0001), forced expiratory volume per second (FEV1, 93.8 ± 0.5% pred, P < 0.0001) and FEV1/FVC (0.792 ± 0.003, P < 0.0001) compared with the other groups. Linear regression showed that HbA1c was closely related to FVC (β = -6.972154, P < 0.0001) and FEV1 (β = -5.591589, P < 0.0001), but not to FEV1/FVC. Logistic regression analysis revealed a significant association between HbA1c and a restrictive spirometric pattern (FVC < 80% pred., FEV1/FVC ≥ 0.70; OR = 3.772, 95% CI = 1.234-11.53), indicating that elevated HbA1c is closely associated with lung impairment in the non-diabetic population. In the healthy population, relatively high HbA1c level is associated with decrements of FVC and FEV1 and may be a reliable predictor of poor lung function, especially the restrictive pattern.

Physical Activity in School-Age Children Born Preterm

To compare objectively measured physical activity in 11- and 15-year-old children who were born preterm with term-born controls and related physical activity measures to lung function measures. We used data from the Avon Longitudinal Study of Parents and Children. We compared total physical activity, moderate-to-vigorous physical activity, and sedentary behavior between children born at 25-32, 33-34, 35-36, and 37-43 weeks' gestation at ages 11 and 15 years. At age 11 years, physical activity measures were correlated with lung spirometry recorded at age 7-9 years. Valid physical activity data at age 11 years were available for 5025, 197, 57, and 48 children born at 37-43, 35-36, 33-34, and 25-32 weeks' gestation, respectively. At age 15 years, valid physical activity data were available for 1829, 62, 32, and 24 children born at 37-43, 35-36, 33-34, and 25-32 weeks' gestation. Boys were more physically active than girls at both ages. There were no differences in total physical activity, moderate-to-vigorous physical activity, or sedentary behavior in children between the different gestation groups. Physical activity at age 11 years did not correlate with spirometry measures at age 7-9 years. Physical activity was similar for the different gestational groups and did not correlate with lung spirometry. Physical activity does not appear to be limited in preterm-born children despite lung function deficits noted in childhood.

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.

Lung function, airway remodeling, and inflammation in infants: outcome at 8 years

BackgroundAssociations between early deficits of lung function, infant airway disease, and outcome at school age in symptomatic infants are still unclear. ObjectiveTo report follow-up data on a unique cohort of children investigated invasively in infancy to determine predictive value of airway disease for school-aged respiratory outcomes. MethodsFifty-three infants previously studied using bronchoscopy and airway conductance were approached at 8 years of age. Symptoms, lung volumes, and airway responsiveness were reassessed. Data on lifetime purchase of asthma medication were obtained. Lung function was compared with that of 63 healthy nonasthmatic children. ResultsForty-seven children were reevaluated. Physician-diagnosed asthma was present in 39 children (83%). Twenty-five children (53%) had current and 14 children (30%) had past asthma. No pathologic feature in infancy correlated with any outcome parameter. As expected, study children had significantly reduced lung function and increased airway responsiveness compared with healthy controls, and very early symptoms were risk factors for reduced lung function. Current asthma was associated with reduced infant lung function and parental asthma. Reduced lung function in infancy was associated with purchase of inhaled corticosteroids when 6 to 8 and 0 to 8 years of age. ConclusionThe lack of predictive value of any pathologic measure in infancy, reported here for the first time to our knowledge, demonstrates that pathologic processes determining the inception of asthma, which are as yet undescribed, are different from the eosinophilic inflammation associated with ongoing disease.

Intrauterine and early postnatal exposure to outdoor air pollution and lung function at preschool age

BackgroundEffects of prenatal and postnatal exposure to air pollution on lung function at preschool age remain unexplored. We examined the association of exposure to air pollution during specific trimesters of...

Asthma, airflow limitation and mortality risk in the general population.

Asthma and chronic obstructive pulmonary disease co-exist in a significant proportion of patients. Whether asthma increases mortality risk among subjects with airflow limitation remains controversial. We used data from 2121 adult participants in the population-based Tucson Epidemiological Study of Airway Obstructive Disease cohort. At enrolment (1972-1973), participants completed questionnaires and lung function tests. Participants were categorised into four groups based on the combination of airflow limitation (AL; forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <70%) and physician-confirmed asthma at baseline. Vital status as of January 2011 was assessed through the National Death Index. Cox proportional hazards models were used to test differences in mortality risk across the four airflow limitation/asthma groups. In multivariate Cox models, the AL+/asthma+ group had a 114% increased mortality risk during follow-up compared with the AL-/asthma- group (adjusted HR 2.14; 95% CI 1.64-2.79). The corresponding hazard ratios were 1.09 (95% CI 0.89-1.34) and 1.34 (95% CI 1.14-1.57) for the AL-/asthma+ and AL+/asthma- groups, respectively. Among subjects with airflow limitation, asthma was associated with increased mortality risk (HR 1.58, 95% CI 1.17-2.12). However, this increased risk was substantially reduced and no longer significant after further adjustment for baseline FEV1 levels. Similar results were obtained when airflow limitation was defined as FEV1/FVC less than the lower limit of normal. In a population-based cohort, subjects with concomitant airflow limitation and asthma had an increased risk of dying, which was mainly related to their baseline lung function deficits.

Lung development in the late preterm

An increasing incidence of moderate-to-late prematurity is observed worldwide (6-7% of all births). Moderate-to-late prematurity is a cause of important mortality and morbidity, even when it is just a few weeks before term gestation [1]. Respiratory issues related to moderate prematurity include delayed neonatal transition to air breathing, respiratory distress resulting from delayed fluid clearance, surfactant deficiency, and pulmonary hypertension. There is increasing evidence to support the hypothesis that preterm delivery, even in the absence of any neonatal respiratory disease, may have adverse effects on subsequent lung growth and development, and that these alterations may persist during the early years of life. Premature birth interrupts normal in utero lung development and results in an early transition from the hypoxic intrauterine environment to a comparatively hyperoxic atmospheric environment [2]. Alveolar walls may be thicker, impairing optimal gas exchange. Colin et al. proposed that preterm birth leads to decreased parenchyma elasticity and subsequent airway tethering, a mechanism by which airway wall compliance keeps surrounding alveoli well opened [3]. The long-term significance of reduced airway function early in life has been emphasized in a longitudinal study involving a large group of non-selected infants who had participated in the Tucson Children’s Respiratory study [4]. In this study Stern et al. showed that infants whose pulmonary function was in the lowest quartile also had pulmonary function in the lowest quartile through the years of follow-up until early adulthood. These findings in a normal unselected population, suggest that the level of pulmonary function in early life tracks and changes little with growth. Several authors suggest that deficits in lung function during early life, especially if associated with lower respiratory illnesses, increase the risk of chronic obstructive pulmonary disease in late adult life [5-7]. Of particular importance in this context may be the role played by RSV, which affects most children during their first year of life. The risk of life-threatening RSV infection appears relevant up to a post-conceptional age of 44 weeks. Stein et al. reported that RSV lower respiratory tract illness during the first 3 years of life in a healthy birth cohort was associated with recurrent wheeze up to age 11 [8]. In conclusion altered lung development is a characteristic feature of the late preterm infants and its impact on neonatal and postnatal morbidity needs to be considered.

Disrupted lung development and bronchopulmonary dysplasia: opportunities for lung repair and regeneration.

Advances in medical therapy have increased survival of extremely premature infants and changed the pathology of bronchopulmonary dysplasia (BPD) from one of acute lung injury to a disease of disrupted lung development. With this evolution, new questions emerge regarding the molecular mechanisms that control postnatal lung development, the effect of early disruptions of postnatal lung development on long-term lung function, and the existence of endogenous mechanisms that permit lung regeneration after injury. Recent data demonstrate that a significant component of alveolarization, the final stage of lung development, occurs postnatally. Further, clinical and experimental studies demonstrate that premature birth disrupts alveolarization, decreasing the gas exchange surface area of the lung and causing BPD. BPD is associated with significant short-term morbidity, and new longitudinal, clinical data demonstrate that survivors of BPD have long-standing deficits in lung function and may be at risk for the development of additional lung disease as adults. Unfortunately, current care is mainly supportive with few effective therapies that prevent or treat established BPD. These studies underscore the need to further elucidate the mechanisms that direct postnatal lung growth and develop innovative strategies to stimulate lung regeneration. Despite significant improvements in the care and survival of extremely premature infants, BPD remains a major clinical problem. Although efforts should remain focused on the prevention of preterm labor and BPD, novel research aimed at promoting postnatal alveolarization offers a unique opportunity to develop effective strategies to treat established BPD.

The Concentration of Iron in Real-World Geogenic PM10 Is Associated with Increased Inflammation and Deficits in Lung Function in Mice

BackgroundThere are many communities around the world that are exposed to high levels of particulate matter <10 µm (PM10) of geogenic (earth derived) origin. Mineral dusts in the occupational setting are associated with poor lung health, however very little is known about the impact of heterogeneous community derived particles. We have preliminary evidence to suggest that the concentration of iron (Fe) may be associated with the lung inflammatory response to geogenic PM10. We aimed to determine which physico-chemical characteristics of community sampled geogenic PM10 are associated with adverse lung responses.MethodsWe collected geogenic PM10 from four towns in the arid regions of Western Australia. Adult female BALB/c mice were exposed to 100 µg of particles and assessed for inflammatory and lung function responses 6 hours, 24 hours and 7 days post-exposure. We assessed the physico-chemical characteristics of the particles and correlated these with lung outcomes in the mice using principal components analysis and multivariate linear regression.ResultsGeogenic particles induced an acute inflammatory response that peaked 6 hours post-exposure and a deficit in lung mechanics 7 days post-exposure. This deficit in lung mechanics was positively associated with the concentration of Fe and particle size variability and inversely associated with the concentration of Si.ConclusionsThe lung response to geogenic PM10 is complex and highly dependent on the physico-chemical characteristics of the particles. In particular, the concentration of Fe in the particles may be a key indicator of the potential population health consequences for inhaling geogenic PM10.