Relationship between birth weight, maternal smoking during pregnancy and childhood and adolescent lung function: A path analysis.

BACKGROUND: Low birth weight and gestational maternal smoking have been linked with reduced lung function in children in many cross sectional studies. However, these associations have not yet been assessed with repeated measurements of lung function. Our aim was to investigate the effects of birth weight, gestational age, and gestational maternal smoking on lung function in children at age 10 and 18 years. METHODS: In the Isle of Wight birth cohort spirometry was performed at age 10 and 18 years. Information on birth weight and gestational age were obtained from hospital records. Mothers were asked about smoking during pregnancy. We employed linear mixed models to estimate the effect of these risk factors on repeated measurements of lung function. We considered maternal asthma, sex, neonatal intensive care unit admission, height, socio-economic status, personal smoking in participants at age 18, body mass index and environmental tobacco smoke exposure as potential confounders. Finally, we used path analysis to determine links between birth weight, gestational age and gestational maternal smoking on lung function at age 10 and 18 years. RESULTS: Linear mixed models showed that with every 1 kg increase in birth weight, Forced expiratory volume in one second (FEV1) increased by 42.6 ± 17.2 mL and Forced expiratory flow between 25% and 75% (FEF25-75) of Forced vital capacity (FVC) increased by 95.5 ± 41.2 mL at age 18 years after adjusting for potential confounders. Path analysis suggested that birth weight had positive direct effects on FEV1 and FEF25-75 and positive indirect effect on FVC at 10 years which were carried forward to 18 years. Additionally, results also suggested a positive association between gestational age and FEV1, FVC and FEF25-75 at ages 10 and 18 years and an inverse association between gestational smoke exposure and FEV1/FVC ratio and FEF25-75 at age 18 years. CONCLUSIONS: Higher birth weight and gestational age were associated with higher FEV1, FVC and FEF25-75 and maternal smoking during pregnancy was associated with reduced FEV1/FVC ratio and FEF25-75. The use of path analysis can improve our understanding of underlying "causal" pathways among different prenatal and childhood factors that affect lung function in both pre-adolescent and adolescent periods.

Relation of lung function and current inhalant allergen-specific immunoglobulin E concentrations in adolescents (GINIplus cohort).

BACKGROUND: The prevalence of allergen sensitization reaches up to 46.6% in 14- to 17-year-old German adolescents. Polysensitization is strongly associated with a higher risk of allergic rhinitis or asthma. Whether or how sensitization also is related to lung function remains uncertain. OBJECTIVE: To assess whether sensitization to common inhalant allergens is associated with lung function in adolescents after stratification by allergic respiratory disease. METHODS: In total, 1,719 15-year-old participants of the German Infant Study on the Influence of Nutrition Intervention plus Air Pollution and Genetics on Allergy Development (GINIplus) birth cohort provided valid spirometric indices, including forced expiratory volume in 1 second, forced vital capacity (FVC), forced expiratory flow rate at 25% to 75% of the FVC, and specific immunoglobulin E (IgE) screening test to 8 inhalant allergens (ImmunoCAP). Complete information on allergic rhinitis and asthma status was available for 1,128 subjects. Associations between lung function parameters and sensitization, classified into 4 groups (no sensitization to polysensitization) were analyzed using adjusted linear regression models. RESULTS: Among participants, 21.1% (n = 347) had allergic rhinitis, 10.1% (n = 119) had asthma, and 46.4% (n = 798) had a positive screening test to inhalant allergens. Prevalences were consistently higher in boys. The percentage of subjects with rhinitis or asthma increased from 5.8% in non-sensitized subjects (n = 620) to 69.4% in polysensitized subjects (n = 144). Sensitization was not associated with any spirometric parameter considered in subjects with allergic rhinitis, asthma, or neither disease. CONCLUSION: Although allergen-specific IgE concentrations can contribute to the identification of subjects at higher risk for allergic rhinitis and asthma, sensitization to inhalant allergens is not related to impaired spirometric lung parameters within the different allergic respiratory disease subgroups.

FVC deterioration, airway obstruction determination, and life span in Ataxia telangiectasia.

RATIONALE: Forced vital capacity (FVC) values decrease with progress of the disease in Ataxia telangiectasia (AT). OBJECTIVE: To study the effect of this process on airway obstruction determination and life span in AT. METHODS: Clinical data and yearly best spirometry maneuvers were collected retrospectively from 37 AT patients (196 spirometry tests) during 5.4 ± 1.8yrs (initial age 4-21 y). Twelve patients were walking (7 of them had recurrent respiratory system infections); 25 subjects were confined to wheelchair, of them 8 patients were towards end-stage lung disease. Spirometry indices included Forced Vital Capacity (FVC), mid-expiratory-flow (FEF25-75), and tidal volume (VT). We calculated FEF25-75/FVC and VT/FVC ratios. RESULTS: FVC declined from 67 ± 8 while walking to 19 ± 6 %predicted values. FEF25-75 values that were elevated (116 ± 23 %predicted) while walking, decreased to 69 ± 27 %predicted at end-stage where 7 patients responded to bronchodilators. VT/FVC ratio was 0.25 ± 0.06 while walking, increased to 0.35 once on wheelchairs, and further increased to 0.57 ± 0.19 at end-stage disease. FEF25-75/FVC ratio was 2.54 ± 0.70 above normal (∼1.0) increasing to 4.16 ± 0.75 at end stage. A sharp elevation was seen in FEF25-75/FVC ratio when FEV1 was still ∼45 %predicted and 2-years prior to death. CONCLUSIONS: Having a low baseline-FVC (60% predicted) artificially raises FEF25-75 values, so FEF25-75 of "mild obstruction" values may indicate severe airway obstruction in AT subjects. VT/FVC and FEF25-75/FVC ratios may therefore assist in revealing higher than normal breathing effort. The results further suggest adding VT/FVC and FEF25-75/FVC ratios to pulmonary function assessments in patients with AT.

Evolution of lung function during the first year of life in newborn screened cystic fibrosis infants.

RATIONALE: Newborn screening (NBS) for cystic fibrosis (CF) allows early intervention. Design of randomised controlled trials (RCT) is currently impeded by uncertainty regarding evolution of lung function, an important trial end point in such infants. OBJECTIVE: To assess changes in pulmonary function during the first year of life in CF NBS infants. METHODS: Observational longitudinal study. CF NBS infants and healthy controls were recruited between 2009 and 2011. Lung Clearance Index (LCI), plethysmographic lung volume (plethysmographic functional residual capacity (FRCpleth)) and forced expired volume (FEV0.5) were measured at 3 months and 1 year of age. MAIN RESULTS: Paired measurements were obtained from 72 CF infants and 44 controls. At 3 months, CF infants had significantly worse lung function for all tests. FEV0.5 improved significantly (0.59 (95% CI 0.18 to 0.99) z-scores; p<0.01) in CF infants between 3 months and 1 year, and by 1 year, FEV0.5 was only 0.52 (0.89 to 0.15) z-scores less than in controls. LCI and FRCpleth remained stable throughout the first year of life, being on average 0.8 z-scores higher in infants with CF. Pulmonary function at 1 year was predicted by that at 3 months. Among the 45 CF infants with entirely normal LCI and FEV0.5 at 3 months, 80% remained so at 1 year, while 74% of those with early abnormalities remained abnormal at 1 year. CONCLUSIONS: This is the first study reporting improvements in FEV0.5 over time in stable NBS CF infants treated with standard therapy. Milder changes in lung function occurred by 1 year than previously reported. Lung function at 3 months predicts a high-risk group, who should be considered for intensification of treatment and enrolment into RCTs.

Effects of complete dentures on respiratory performance: spirometric evaluation.

OBJECTIVES: There is a lack of data regarding whether edentulous subjects should remove dentures during spirometric measurements or not. The purpose of this study is to determine influences of complete dentures on spirometric parameters in edentulous subjects. MATERIALS AND METHODS: A total of 46 complete denture wearers were included in this study. Respiratory functions of the subjects were evaluated by spirometric tests that were performed in four different oral conditions: without dentures (WOD), with dentures, lower denture only and upper denture only. Forced vital capacity (FVC), peak expiratory flow, forced expiratory volume in 1 s and forced expiratory flow between 25% and 75% were evaluated. The data were analyzed with Friedman, Wilcoxon and paired-samples t tests (α = 0.05). RESULTS: Significant differences were found between spirometric parameters in different oral conditions (p < 0.05). In all spirometric parameters, the most important significant differences were found between conditions WOD, FVC and with lower dentures (FVC), and WOD (forced expiratory volume in 1 s) and with upper dentures (forced expiratory volume in 1 s) (p < 0.001). CONCLUSION: It was observed that complete dentures may unfavourably affect spirometric values of edentulous subjects. However, current findings need to be confirmed with advanced respiratory function tests.

Forced expiratory decay in asthmatic preschool children--is it adult type?

BACKGROUND: The forced expiratory decay in healthy preschool children portrays a convex shape that differs from the linear decay in the older healthy population. The "adult-type" expiratory decay during airway obstruction is concave. The study objective was to determine if the expiratory decay in young asthmatic children is "adult-type". METHODS: Among 245 children (age 3-7 yrs), 178 had asthma (asthmatics) and 67 were non-asthmatic (controls). The expiratory flow decay was inspected by FEF25-75/FVC ratio (=1.0 when linear). Values were compared to those of our formerly studied (n = 108) healthy children. A meaningful obstruction in FEF25-75/FVC ratio was defined as 2-zScores from healthy. A meaningful response to bronchodilators was related to non-asthmatics. RESULTS: In healthy subjects FEF25-75/FVC ratio declined with age from 1.73 ± 0.17 to 1.28 ± 0.11. Non-asthmatics portrayed ratio values similar to those of healthy subjects. In asthmatics, 118/178 displayed a convex to linear expiratory decay (FEF25-75/FVC = 1.33 ± 0.22). Sixty/178 asthmatics portrayed concavity (FEF25-75/FVC-0.79 ± 0.16) that appeared when FEF50 was 43.4 ± 12%healthy. Concavity appearance was also age-dependent (30.4% of 3-4 y old and 59.1% of 6-7 y). Vital-Capacity decreased in either decays, forming a visually petit curve. Most asthmatic children respond to bronchodilators by a meaningful elevation in FEF25-75/FVC values and by a visual change in the shape of the curve. Other common spirometry indices also increased meaningfully. CONCLUSION: Most asthmatic preschool children portray convex to linear expiratory decay with diminished vital-capacity, resulting in a visually smaller than healthy curve, with seemingly normal expiratory decay. These curves may be misinterpreted as "normal" or as "no-cooperation" and may lead to misinterpretation. In response to bronchodilators, FEF25-75/FVC value increases in asthmatics and the curve changes from concave to linear or from linear to convex contour.

Impaired spirometry may suggest sensitization.

The present study confirms that sensitization is very frequent in the general population and suggests that impaired FEF25-75 may be a marker of sensitization. Therefore, when spirometry is abnormal, mainly concerning FEF25-75, sensitization should be suspected.

Impaired FEF25-75 may predict high exhaled nitric oxide values in children with allergic rhinitis and/or asthma.

Allergic rhinitis and asthma are closely associated. Inflammation is a common pathological characteristic shared by both disorders. The measure of the fractional concentration of exhaled nitric oxide (FeNO) may be considered a surrogate marker for airway inflammation. Forced expiratory flow between 25 and 75 percent of vital capacity (FEF25-75) has been previously demonstrated to be able to predict BHR and bronchial reversibility. The aim of this study was to evaluate whether impaired FEF25-75 values may be related to FeNO values in a pediatric cohort of allergic subjects. 850 children with allergic rhinitis, allergic asthma, or both, were evaluated. Bronchial function (FEV1, FVC, and FEF25-75), FeNO, and sensitizations were assessed. Bronchial function and FeNO were significantly different in the 3 groups (p less than 0.001). A strong inverse correlation between FeNO and FEV1was found in patients with rhinitis, asthma and asthma with rhinitis (r= -0.72, r=-0.70 and r= -0.70, respectively). Impaired FEF25-75 values (such as less than 65 percent of predicted) were significantly associated with high FeNO levels (such as =34 ppb). In conclusion, this study provided evidence that FEF25-75 is strongly and inversely related with FeNO and FEF25-75 may predict high FeNO levels in children with allergic rhinitis, asthma or both.

Impaired FEF25-75 values may predict bronchial reversibility in allergic children with rhinitis or asthma.

FEV1 is considered an important parameter for asthma diagnosis and follow-up. However, it has been proposed that FEF25-75 could be more sensitive than FEV1 to detect slight airways obstruction. Bronchial reversibility defined by positive response to bronchodilation test. The aim of the present study was to define whether an impaired FEF25-75 value (less than 65 percent of predicted) may be predictive for reversibility in a large cohort of allergic children with rhinitis or asthma. Six hundred allergic children were recruited: 300 with controlled asthma and 300 with allergic rhinitis. All of them were evaluated by performing spirometry, bronchodilation test, and skin prick test. Two predictors were significantly associated with bronchial reversibility: i) an impaired FEF25-75 value (less than 65 percent of predicted), and ii) sensitization to perennial allergens. It was more relevant in children with rhinitis (ORAdj:8.9 and 2.2 respectively). In conclusion, this study, conducted in real life, could suggest that an impaired FEF25-75 value (less than 65 percent of predicted) may be considered a reliable marker of bronchial reversibility, mainly in children with allergic rhinitis.

Lung Clearance Index and HRCT are complementary markers of lung abnormalities in young children with CF.

RATIONALE: High resolution computed tomography (HRCT) is a more sensitive tool for detecting early cystic fibrosis (CF) lung disease than either spirometry or plain radiography, but its relationship to other measures of lung function has not been established in young children. OBJECTIVES: (1) To assess whether the lung clearance index (LCI) derived from multiple breath inert-gas washout (MBW) is as effective as HRCT in identifying pulmonary abnormalities; and (2) explore the relationships between abnormalities detected by HRCT and by spirometry, plethysmography and MBW (collectively, LFTs) in young children with CF. METHODS: Children with CF underwent LFTs and volumetric HRCT on the same day. Healthy age-matched controls underwent identical LFTs without HRCT. Scans were anonymised, and scored using the Brody-II CT scoring system, to assess for presence and extent of bronchiectasis, airway wall thickening, mucus plugging, and parenchymal opacities. RESULTS: Assessments were undertaken in 60 children with CF (mean (SD) 7.8 (1.3 years) and 54 healthy controls (7.9 (1.2) y). Among children with CF, 84% (47/56) had abnormal LCI, 58% (27/47) abnormal plethysmographic lung volumes (FRC(pleth) or RV), 35% (21/60) abnormal sRaw and 47% (28/60) abnormal spirometry (FEV1 or FEF(25-75)); whereas HRCT scans were abnormal in 85% (51/60): median total Brody-II score: 9.5% (range 0-51%). Total CT score correlated more strongly with LCI (Spearman correlation = 0.77) than with spirometry (R = -0.43) or any other marker of lung function. Of the nine children with normal LCI, five had abnormalities on HRCT, whereas five children with normal HRCT had raised LCI. CONCLUSIONS: These results suggest that while LCI and HRCT have similar sensitivity to detect CF lung disease, complimentary information may be gained in individual patients.

Salivary profile and oxidative stress in children and adolescents with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is characterized by altered exocrine secretions; however, no comprehensive compositional profile of CF serous and mucous saliva secretions has been published. DESIGN: We analyzed salivary flow rate and composition, and oxidative stress-related parameters, comparing CF patients with non-CF bronchiectasis patients and the healthy controls. RESULTS: Median salivary magnesium concentration and lactate dehydrogenase activity were significantly lower in CF patients than in the healthy controls. Salivary total protein concentration was 45% higher in CF patients than in non-CF bronchiectasis patients. CF patients showed 8% lower levels of peroxidase compared with non-CF bronchiectasis. Salivary total antioxidant status, superoxide dismutase and uric acid values in the CF group were higher by 15%, 35% and 31%, respectively, than in both control groups. CONCLUSIONS: Cystic fibrosis patients demonstrated altered salivary profile, especially in antioxidant enzymatic and molecular activity, possibly resulting from the oral cavity's ongoing inflammatory and oxidative process. Free radical mechanisms may be involved in CF pathogenesis.

Effect of ciclesonide on bronchial asthma in athletes.

BACKGROUND: Although it is well established that the incidence of bronchial asthma is higher in the athlete population than in the general population, little information exists about the efficacy of treatment of bronchial asthma in the athlete population. OBJECTIVES: We conducted this study with the objective of determining the efficacy of treatment of bronchial asthma in an athlete population living in Niigata Prefecture, Japan. METHODS: We conducted a retrospective study of bronchial asthma in an athlete population. Athletes diagnosed as having asthma, based on the Global Initiatives for Asthma (GINA) guidelines, who visited the Niigata Institute for Health and Sports Medicine between January 2007 and June 2008 were enrolled in this study. We compared two groups of patients, a group treated with ciclesonide (CIC) alone and another treated with montelukast alone, with the treatment duration lasting at least 3 months in both groups. The CIC or montelukast groups were compared in terms of the clinical symptoms, pulmonary function parameters, and fraction of exhaled nitric oxide (FENO). RESULTS: There were no significant differences in the sex distribution, age, frequency of symptoms, pulmonary function parameters, or other examination data before treatment between the CIC and montelukast groups. The CIC group tended to show better symptom control and to need fewer changes of treatment than the montelukast group. While improvements of the pulmonary function parameters and FENO values were observed in the CIC group, no significant changes of these parameters were observed in the montelukast group. CONCLUSIONS: These data suggest that CIC offers greater promise for the control of asthma than montelukast in the athlete population, although further investigation is required.

T cells in sputum of asthmatic patients are activated independently of disease severity or control.

BACKGROUND: T cells play an important role in bronchial asthma. Although airway CD4+ T cells have been extensively studied previously, there are hardly any studies relating CD8+ T cell activation and disease symptoms. OBJECTIVES: The aim of this study was to analyse the association between T cell activation in induced sputum T cells and asthma severity and control; and to evaluate T cell subpopulations in the same subgroups. METHODS: Fifty allergic asthmatic patients were recruited and lung function testing was performed. Airway cells were obtained by sputum induction via inhalation of hypertonic saline solution. CD3, CD4, CD8, CD28, CD25 and CD69 were studied by flow cytometry in whole induced sputum and peripheral blood cells. RESULTS: Total induced sputum T cells and CD8+ T cells had a higher relative percentage of the activation markers CD25 and CD69 in comparison with peripheral blood. In sputum, the relative percentage of CD25 was higher in CD4+ T cells when compared to CD8+ T cells and the reverse was true regarding CD69. However, neither disease severity nor control were associated with the relative percentage of CD25 or CD69 expression on T cells in sputum. CONCLUSIONS: Both CD4+ and CD8+ T cells are activated in the lungs and peripheral blood of asthmatic patients. However, with the possible exception of CD69+ CD8+ T lymphocytes in the sputum, there is no association between T cell activation phenotype in the target organ and disease severity or control.

Identifying uncontrolled asthma in young children: clinical scores or objective variables?

OBJECTIVE: Several international asthma guidelines emphasize the importance of assessing asthma control. However, there is limited data on the usefulness of available assessment tools in indicating disease control in young asthmatics. This study investigated the ability of Chinese version of Childhood Asthma Control Test (C-ACT) and other disease-related factors in identifying uncontrolled asthma (UA) in young children. METHODS: During the same clinic visit, asthma patients 4 to 11 years of age completed C-ACT and underwent exhaled nitric oxide and spirometric measurements. Blinded to these results, the same investigator assigned Disease Severity Score (DSS) and rated asthma control according to Global Initiative for Asthma. RESULTS: The mean (SD) age of 113 recruited patients was 9.1 (2.0) years, and 35% of them had UA. C-ACT, DSS and forced expiratory volume in 1 second (FEV(1)) differed among patients with different control status (p < 0.001 for C-ACT and DSS; p = 0.014 for FEV(1)). Logistic regression confirmed that UA was associated with DSS (p < 0.001), PEF (p = 0.002), C-ACT (p = 0.011), and FEV(1) (p = 0.012). By ROC analysis, C-ACT and DSS were the best predictors for UA (p < 0.001), followed by PEF (p = 0.006) and FEV(1) (p = 0.007). When analyzed by the Classification and Regression Tree (CART) approach, the sequential use of DSS and C-ACT had 77% sensitivity and 84% specificity in identifying UA. CONCLUSIONS: C-ACT is better than objective parameters in identifying young Chinese children with UA.

Determining the time to maximal bronchodilator response in asthmatic children.

BACKGROUND: The interval between bronchodilator administration and post-bronchodilator lung function testing is critical for accurate interpretation of the bronchodilator response. The time course of this response in children is not well documented. We aimed to document the time taken to achieve maximal lung function following salbutamol inhalation. METHODS: Eighteen asthmatic children between 7 and 18 years of age with a history of bronchodilator responsiveness were recruited. Spirometry was performed before and at 0, 10, 15, 20, 40, 60, and 90 minutes after salbutamol inhalation 600 microg (Ventolin; GlaxoSmithKline) via a spacer (Volumatic; GlaxoSmithKline). RESULTS: Spirometric indices significantly increased after salbutamol inhalation (p < 0.001). The group median time to maximal response in forced expiratory volume in 1 second (FEV(1)) was 17.5 (10-60: 10th-90th centiles) minutes after salbutamol. The magnitude of group response in FEV(1) was significantly higher at 15 and 20 minutes than at 0 and 10 minutes post-salbutamol inhalation (repeat measures analysis of variance [ANOVA] on ranks; p < 0.05). CONCLUSION: We conclude that a minimal interval of 20 minutes, before re-testing spirometry, is required to document the maximal response to bronchodilators in the majority of asthmatic children.

Periodontitis as a potential risk factor for chronic obstructive pulmonary disease: a retrospective study.

AIMS AND OBJECTIVES: A relationship between poor periodontal health and respiratory disease has been suggested by a number of recent studies. The present study was undertaken to evaluate potential association between respiratory diseases and periodontal health status and to co-relate the severity of periodontal disease with that of chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: 150 patients of COPD (test group) and 50 Patients without COPD (control group) were recruited for the study. Information regarding patient's demographic and socioeconomic status and lifestyle (history of smoking) were considered in the study. Patients with COPD were grouped into mild, moderate and severe category on the basis of Spirometry. Periodontal health was assessed by measuring probing pocket depth, Clinical Attachment Loss (CAL) and Oral Hygiene Index (OHI). RESULTS: The results showed that the subjects with COPD had significantly more mean CAL) and a higher mean OHI than those without COPD. The risk for COPD appeared to be significantly elevated when attachment loss was found to be severe. A trend was noted in that lung function appeared to diminish as the amount of attachment loss increased. CONCLUSION: On the basis of the observed results of the study it can be concluded that the risk for COPD appeared to be significantly elevated when attachment loss was found to be severe. It is conceivable that oral interventions that improve oral health status may prove to lower the severity of lung infection in susceptible populations.

Pulmonary dysanapsis and diving assessments.

Airway obstruction is a relative contraindication to diving. Dive candidates are assessed clinically, and lung function tests evaluate variables such as forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and the FEV1/FVC ratio. A small number of individuals have a normal FEV1, but a disproportionately large lung capacity, or pulmonary dysanapsis. These individuals have a decreased FEV1/FVC ratio, suggesting airway obstruction, which may affect their dive medical assessments. Three cases of pulmonary dysanapsis presented for fitness-to-dive assessment. Case 1, a 29-year-old male had an FEV1: 3.52 L (85% predicted), FVC: 5.31 L (108.5% predicted), giving a FEV1/FVC of 66%. Case 2, a 25-year-old male with an FEV1: 4.55 L (95% predicted), FVC: 7.0 L (121% predicted) and a FEV1/FVC of 66%. Albuterol produced an FEV1 increase of 11%, but his hypertonic saline challenge was negative. Case 3, a 61-year-old man had an FEV1: 3.49 L (126% predicted), FVC: 7.06 L (216% predicted), and a FEV1/FVC of 49%. This report highlights pulmonary dysanapsis which may be confused with obstructive airway disease and applicants deemed unfit to dive. While pulmonary dysanapsis may increase the risk of airway hyperresponsiveness, there is no evidence of an association with diving-related pulmonary barotrauma.