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Background: Abnormal weights, eg, obesity, has shown a strong modifying effect on the association between air pollution exposure and lung function impairment in adults., Research Question: How might weight status modify the effects of long-term air pollution exposure on adolescents' lung function, particularly in areas with pollution levels much lower than the current European Union (EU) air quality standards?, Study Design and Methods: In this observational study, we investigated 2,224 adolescents from the German Infant Study on the Influence of Nutrition Intervention Plus Environmental and Genetic Influences on Allergy Development and the Influence of Life Style Factors on the Development of the Immune System and Allergies in East and West Germany birth cohorts. Lung function was measured at age 15 years. Underweight, normal weight, and overweight or obese were defined using percentiles of BMI. Average concentrations of air pollution were modelled at residential addresses at four exposure windows between 0 and 15 years. Multivariate linear regression models were fitted by weight group on lung function with exposure at each window or cumulative exposure since birth., Results: The median air pollution concentrations were half to two-thirds of the EU standards. Significant associations were observed only for individuals who were underweight and overweight or obese. For example, per interquartile range increase in nitrogen dioxide at the 15-year exposure window, FEV 1 declined by -2.9% (95% CI, -5.2% to -0.5%) for the underweight group and -3.4% (95% CI, -5.4% to -1.2%) for the overweight or obese group. Similarly, longer exposure to moderate-level air pollution since birth was associated significantly with lung function impairment for groups with abnormal weight., Interpretation: Exposure to low to moderate levels of air pollution was associated with lung function impairment for adolescents with abnormal weight. Longer exposure aggravated the adverse effect. Whether a critical exposure window since birth exists warrants further exploration., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

A hallmark of the newly published GLI (Global Lungs Initiative) spirometric reference values is their "all-age" (3-95yr) predictive power, accomplished by incorporating non-linear age dependencies into modelling parameters. This modelling strategy is especially promising for the age range of puberty; however, the performance of GLI-values for adolescents is currently unknown. We calculated GLI-based z-scores for children/adolescents without apparent respiratory diseases from two different German studies, LUNOKID (N = 1943, 4-19 years) and GINIplus (N = 1042, 15 years) and determined the goodness of fit for specific age groups. We defined fit sufficient if the absolute mean of z-scores was <0.5. For children (<10yr) the mean GLI-based z-scores for FEV1 and FVC reached a good fit with mean z-scores for FEV1 between -0.11 and 0.01 and mean z-scores for FVC between 0.01 and 0.16, but larger deviations were observed in adolescents, especially boys (mean z-score -0.58 for FEV1 and -0.57 for FVC in GINIplus). The fit for FEV1/FVC was sufficient. GLI reference values provided reasonable estimates for the individuals enrolled in our studies, which span the age range of lung growth and development. However, we found that GLI-predictions overestimated lung volumes, especially those for German adolescent boys, which may, left unrecognised, lead to erroneous diagnosis of lung disease. Caution should be taken when applying these reference values to epidemiologic studies.

Patients with alpha-1-antitrypsin deficiency (AATD) and a PI-ZZ genotype are at high risk to develop severe emphysema during adulthood. However, little is known about early stages of emphysema and disease manifestation in other PI-types. Spirometry is commonly used for monitoring although early manifestation of emphysema is suspected within the peripheral airways that are not accessible by forced expiratory manoeuvres. We hypothesized that the Lung Clearance Index (LCI) derived from multiple breath nitrogen-washout (N2-washout) is useful to bridge this diagnostic gap. Patients from age 4 years onward and different PI-types performed N2-washout and spirometry. Results were compared to controls. 193 patients (4-79 years, 75% PI-ZZ) and 33 controls (8-60 years) were included. Mean (SD) LCI in patients was 9.1 (3.1) and 6.3 (0.6) in controls (p ≤ 0.001). 47% of adult patients with other than PI-ZZ genotypes and 39% of all patients with normal spirometry had abnormal LCIs. The LCI measured by N2-washout discriminates between patients with AATD and controls, reflects AATD related lung disease in all stages and appears to identify early peripheral lung changes in younger age than spirometry. We conclude that a normal spirometry does not exclude presence of AATD related lung disease even in genotypes other than PI-ZZ., (Copyright © 2016. Published by Elsevier Ltd.)

The current standard for monitoring lung function in children with asthma is spirometry. In Europe, results of these lung function tests have been related to Zapletal reference values published in 1977. Recently, the Global Lung Function Initiative (GLI) published predicted values of spirometry for 5 ethnic groups, valid over an age range from 3 to 95 years. These reference values have been approved by many international lung societies, and the algorithms are increasingly being implemented globally. This report describes the consequences of the transition from Zapletal reference values to GLI reference values for 2 pediatric asthma patients, which include unexpected declines in lung function and the ability to take advantage of newly approved reimbursement for advanced therapy. The Zapletal and GLI reference values cannot be used interchangeably, and transition to the GLI values might lead to better treatment in the future., (Copyright © 2016 by the American Academy of Pediatrics.)

Objectives: Methotrexate may cause severe adverse pulmonary side-effects in adults with rheumatoid arthritis. Our aim was to examine the long-term effect of MTX on lung function in patients with juvenile idiopathic arthritis (JIA)., Methods: We retrospectively reviewed the charts of all 68 patients with JIA treated with MTX at our centre over a 14-year period. Results of annual pulmonary function tests (PFT) were compared using paired t-tests adjusted by Bonferroni correction and by linear regression analysis., Results: The patients in our study had taken MTX for a median of 6.7 years with a median cumulative dose of 3219 mg. In a subgroup of 37 patients PFT had been performed before the onset of MTX. In this subgroup there was a significant decrease of mean mid-expiratory flow (MMEF) after 3 years (-14.0%, p<0.001) of MTX. Diffusion capacity of the lung for carbon monoxide (DLCO) was reduced after the third year (-12.4%, p=0.001). In the total group there was a decrease in MMEF between years 3 and 4 after MTX onset (-13.5%, p=0.001). Forced expiratory volume (FEV1) showed a slight rise between years 4 and 5 (+5.5%, p=0.003). All other parameters remained without significant changes. There was no correlation of PFT results and cumulative MTX dose or JIA subtype. None of our patients developed clinically relevant lung disease., Conclusions: In summary we found some declines of MMEF and DLCO during long-term treatment with MTX. Overall our data confirm the relative safety of long-term MTX treatment in patients with JIA. We conclude that further data on the development of pulmonary function in patients receiving MTX therapy would be helpful.

Lung biopsy is necessary for establishing the diagnosis in patients with otherwise unclassified diffuse or localized parenchymal lung disease. This study aimed to assess the safety and accuracy of video-assisted thoracoscopic (VATS) lung biopsy in children with diffuse parenchymal lung disease (DPLD). In addition we aimed to evaluate the value of this technique with respect to the spectrum of diseases encountered, correlating histological diagnosis with treatment decisions and subsequent clinical outcome. Data from all patients (n = 21) who underwent surgical lung biopsy for suspected DPLD between March 2001 and August 2006 were collected prospectively. Median age was 3 years, 8 months (range 11 days to 15 years, 2 months). All lung biopsies were performed by VATS under general anesthesia. Median operative time was 45 min (range 25-100 min). Conversion to minithoracotomy due to cardiorespiratory difficulties was necessary in two young infants. There were no further intraoperative complications. In 8/21 children, a chest tube was inserted postoperatively for a median of 2 days (range 1-5 days). In one patient, prolonged air-leakage was managed thoracoscopically on postoperative day 9. There were no other postoperative complications. The specimens were of adequate volume and quality and a histopathological diagnosis was obtained for all patients. There was a broad spectrum of different diagnoses which led to specific therapeutic decisions. Subsequent medical treatment was beneficial in the majority of the patients. In conclusion, VATS is a safe and effective procedure for diagnosis of children with suspected DPLD. Diagnostic accuracy is high, morbidity rates are low, and patients may benefit from avoiding thoracotomy., ((c) 2008 Wiley-Liss, Inc.)

Despite the increasing awareness of the need to identify early pulmonary changes in cystic fibrosis (CF) noninvasively, the role of lung function testing in infancy and early childhood remains less clear than in older children with CF. The aim of this review is to summarize available data, discuss the information gained from these publications, and put this information into perspective with more recent developments of lung function testing in both infants and older children with CF. While some of the available data have been the foundation of the current level of understanding of respiratory physiology in CF, interpretation of other data has been hampered by differences between centers with regard to the methods and equipment used, patient selection, small number of subjects, and lack of appropriate reference data. A structured multicenter approach based on recently published recommendations for the measurement of lung function in infancy, together with pursuit of recent developments such as assessment of raised lung volume flow volume curves and ventilation inhomogeneity may help to more effectively utilize lung function tests in infants in the future., (Copyright 2001 Wiley-Liss, Inc.)