Changes In Forced Expiratory Volume In 1s Research Articles

Glycopyrronium/Formoterol: A Review in COPD

Glycopyrronium/formoterol (Bevespi Aerosphere®) is a fixed-dose combination of the long-acting muscarinic antagonist glycopyrronium bromide and the long-acting β2-agonist formoterol fumarate delivered via a pressurized metered dose inhaler (pMDI) and formulated using co-suspension delivery technology. It is approved in the USA and EU for use as maintenance treatment in patients with chronic obstructive pulmonary disease (COPD) and in Japan to relieve symptoms in patients with COPD. In the PINNACLE trials in patients with moderate to very severe COPD, glycopyrronium/formoterol was associated with significantly greater improvements in lung function than its monocomponents and placebo at 24weeks and its monocomponents and open-label tiotropium over 52weeks. In the AERISTO trial, glycopyrronium/formoterol was non-inferior to umeclidinium/vilanterol dry powder inhaler for peak change in forced expiratory volume in 1s (FEV1) within 2h postdose, but not for the change in morning predose trough FEV1, over 24weeks. Glycopyrronium/formoterol was generally well tolerated in patients with moderate to very severe COPD, with most adverse events (AEs) being of mild or moderate severity. Thus, glycopyrronium/formoterol pMDI formulated using co-suspension delivery technology is a useful new addition that extends treatment options for patients with COPD.

Combined effect of central obesity and urinary PAH metabolites on lung function: A cross-sectional study in urban adults.

Central obesity and polycyclic aromatic hydrocarbons (PAHs) exposure were reported as independent risk factors for lung function decline. However, the interaction between central obesity and PAHs exposure on lung function is still unclear. To evaluate the impact of central obesity, urinary polycyclic aromatic hydrocarbon metabolites (OH-PAHs) and their combined effects on lung function in general population. Lung function and urinary OH-PAHs were measured for 3,749 participants from the Wuhan-Zhuhai cohort. Central obesity was evaluated by waist-to-hip ratio. Generalized linear regression was used to estimate combined effect of central obesity and OH-PAHs on lung function. Compared with participants without central obesity and with low urinary total OH-PAHs (∑OH-PAHs) level, those with central obesity and high urinary ∑OH-PAHs level had 59.4 mL and 61.0 mL reductions for forced vital capacity (FVC) and forced expiratory volume in 1s (FEV1), respectively (P < 0.05). The reductions were more evident in smokers and males. Additive interactions between central obesity and urinary ∑OH-PAHs on lung function were observed, especially on FEV1 (P < 0.05). Each 1-unit increase in log-transformed value of ∑OH-PAHs was associated with -34.4 ml (95% confidence interval [CI]: -66.9, -1.8) and -34.8 mL (-61.1, -8.5) changes in FVC and FEV1 among those without central obesity, while -21.4 ml (-49.9, 7.1) and -19.7 ml (-43.4, 4.0) changes among those with central obesity. Polycyclic aromatic hydrocarbons exposure has combined effect with central obesity on lung function parameters.

Effects of ambient temperature on lung function in patients with chronic obstructive pulmonary disease: A time-series panel study

BackgroundLimited evidence concerns the associations between ambient temperature and lung function and the results are mixed. ObjectiveTo evaluate the associations between temperature variations and daily fluctuations in pulmonary function in chronic obstructive pulmonary disease (COPD) patients. MethodsWe designed a time-series panel study of 28 male urban COPD patients with repeated daily lung function measurements from December 2012 to May 2013 in Shanghai, China. We used a linear mixed-effect model combined with a distributed lag model to estimate the cumulative effects of temperature on morning/evening pulmonary function tests (PFTs), including peak expiratory flow (PEF) and forced expiratory volume in 1-s (FEV1), while adjusting for within-subject correlations, individual characteristics, time trends and air pollution levels. ResultsWe obtained a total of 8618 pairs of morning PFTs and 8528 pairs of evening PFTs. The associations between daily mean temperature and PEF were inverted U-shaped with both low and high temperatures significantly reducing morning and evening PEF. Compared with the referent temperature (16°C), the low temperature (1st percentile, −1°C) would result in cumulative decreases of 32.20L/min in morning PEF and 21.15L/min in evening PEF over lags of two weeks. The corresponding decrements at the same lag associated with high temperature (99th percentile, 25°C) were 38.10L/min in morning PEF and 27.08L/min in evening PEF. There were no statistically significant changes in morning or evening FEV1. ConclusionsThis time-series panel study provided robust evidence that both low and high temperatures were significantly associated with decrements in pulmonary function, particularly in PEF.

Effect of GST variants on lung function following diesel exhaust and allergen co-exposure in a controlled human crossover study

BackgroundIsolated exposure to diesel exhaust (DE) or allergen can cause decrements in lung function that are impacted by the presence of genetic variants in the glutathione-S-transferase (GST) family but the effect of GST interactions with DE-allergen co-exposure on lung function is unknown. We aimed to assess the impact of DE and allergen co-exposure on lung function and the influence of GSTM1 or GSTT1 variation MethodsWe used a blinded crossover study design with 17 atopic subjects exposed to filtered air (FA; the control for DE) or DE for 2h. One hour following each exposure to DE or FA, bronchoscopy was performed to deliver a diluent-controlled segmental allergen challenge (SAC). Methacholine challenge and forced expiratory volume in 1s (FEV1) was performed pre-exposure (baseline airway responsiveness) and 24h post-exposure (effect of co-exposure). Additionally, FEV1 was performed hourly after DE/FA exposure and protein carbonyl content was measured in plasma as an oxidative stress marker. ResultsChanges in FEV1 from baseline were dependent on time following allergen exposure. DE, as opposed to FA, led to a significant change in FEV1 at 2h post-allergen exposure in GSTT1 variants only (24.5±19.6% reduction in GSTT1 null individuals vs. 9.2±7.3% reduction in GSTT1 present individuals). Moreover, plasma protein carbonyl level 4h after co-exposure was higher in the individuals who have the GSTT1 null genotype. ConclusionsThis suggests a gene-environment interaction that endangers susceptible populations co-exposed to DE and allergen.

Heightened response of eosinophilic asthmatic patients to the CRTH2 antagonist OC000459.

The CRTH2 antagonist OC000459 has previously been demonstrated to reduce airway inflammation and improve lung function in moderate persistent asthma. A study was conducted to determine the effect of lower once daily doses of OC000459 and to define the phenotype of subjects most responsive to treatment. Adult subjects (percentage of predicted forced expiratory volume in 1s (FEV1 ) 60-85%) were randomized to OC000459 at three dose levels (25mg once daily, 200mg once daily or 100mg twice daily) or placebo for 12weeks (n=117-125 per group, full analysis set). The primary endpoint was the change from baseline in prebronchodilator FEV1 , and secondary endpoints included Asthma Control Questionnaire (ACQ) and Standardised Asthma Quality of Life Questionnaire [AQLQ(S)], and incidence of exacerbations and respiratory tract infections. OC459 caused a significant improvement in FEV1 compared with placebo at a dose of 25mg once daily (P=0.028). A similar increase was observed in the other dose groups, and the mean change in FEV1 in the pooled dose groups at endpoint was 95ml greater than placebo (P=0.024). In a post hoc analysis of atopic eosinophilic subjects with uncontrolled asthma, a mean increase in FEV1 of 220ml was observed compared with placebo (P=0.005). The mean increase in FEV1 was more marked in younger subjects in this group: for subjects aged ≤40years, there was a mean increase of 355ml compared with placebo (P=0.007). Improvements in ACQ and AQLQ(S) were observed in both the full analysis set and the atopic eosinophilic subgroup. There was a lower incidence of exacerbations and respiratory infections in subjects treated with OC000459. There were no drug-related serious adverse events. OC000459 is a safe and effective oral anti-inflammatory agent, which achieved clinically meaningful improvements in lung function and asthma control in allergic asthmatics with an eosinophil-dominant form of the disease. A dose of 25mg given once daily was as effective as the higher doses studied.

Changes in forced expiratory volume in 1 second over time in patients with controlled asthma at baseline

A predominant feature of asthma is an accelerated rate of decline in forced expiratory volume in 1s (FEV1), but data on the variability and factors associated with this change in patients with controlled asthma are largely unknown. 140 patients with controlled asthma were enrolled based on the Global Initiative for Asthma guidelines. We examined the data of a prospective analysis of the association between asthma control and change in FEV1 over time. A 3-year follow-up assessment was completed in 128 patients. The mean rate of change in FEV1 was a decline of 22.2mLyr(-1), with significant variation in the levels of change. The between patient standard deviation for the rate of decline was 34.1mLyr(-1). We next classified the subjects of less than the 25th percentile as rapid decliners, and greater than the 25th percentile as non-rapid decliners. The decrease in the Asthma Control Test score over a 3-year period was higher for rapid decliners than that for non-rapid decliners (p<0.001). The rapid decliner was more likely to be older, to have higher levels of FeNO, and to have had severe exacerbations during the study. Patients with severe exacerbations had a greater annual decline in FEV1 compared to patients with no exacerbations (-13.6 vs. -53.2mLyr(-1), p<0.0001). Among patients with controlled asthma at baseline, the rate of change in FEV1 is highly variable. Severe exacerbations are strongly associated with a rapid loss of lung function.

Prospective external convergence evaluation of two different quality-of-life instruments in lung resection patients

The interpretation of studies on quality of life (QoL) after lung surgery is often difficult owing to the use of multiple instruments with inconsistent scales and metrics. Although a more standardized approach would be desirable, the most appropriate instrument to be used in this setting is still largely undefined. The aim of the study was to assess the respective ability of two validated QoL instruments (European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30/L13 and Short Form (36) Health Survey (SF-36)) to detect perioperative changes in QoL of patients submitted to pulmonary resection for non-small-cell lung cancer (NSCLC). A prospective study on 33 consecutive patients (May 2009-December 2009) was submitted to pulmonary resection. All patients completed both EORTC QLQ-C30 with lung module 13 and SF-36 pre- and postoperatively (3 months). Preoperative changes of all SF-36 and EORTC scales were assessed by using the Cohen's effect-size method. External convergence between different instruments (SF-36 vs EORTC) was assessed by measuring the correlation of scales evaluating the same concepts (physical, psychosocial, and emotional). The correlation coefficients between standardized perioperative changes (effect sizes) of objective functional parameters (forced expiratory volume in 1s (FEV1) and diffusion lung capacity for carbon monoxide (DLCO)) and SF-36 or EORTC scales were also investigated. A poor correlation (r < 0.5) was detected between most of the scales of the two instruments measuring the same QoL concepts, indicating that they may be complementary in investigating different aspects of QoL. Only the SF-36 and EORTC social functioning scales and the SF-36 mental health and EORTC emotional functioning scales had a correlation coefficient >0.5. In general, EORTC was more sensitive in detecting physical or emotional declines but was more conservative in detecting improvements. Both SF-36 and EORTC showed poor correlations (r < 0.5) between perioperative changes in QoL and FEV1 or DLCO, confirming that objective parameters cannot be surrogates to the subjective perception of QoL. In particular, there was a poor correlation between perceived changes in dyspnea and objective changes in FEV1 or DLCO. EORTC behaved similarly to SF-36 in assessing perioperative changes in generic QoL scales, but, with the use of its lung module, provided a more detailed evaluation of specific symptoms. For this reason, EORTC should be regarded as the instrument of choice for measuring QoL in the thoracic surgery setting.

Impact of lobectomy for non-small-cell lung cancer on respiratory function in octogenarian patients with mild to moderate chronic obstructive pulmonary disease☆

To assess the long-term impact of standard lobectomy on respiratory function in octogenarian patients with mild/moderate chronic obstructive pulmonary disease (COPD). We reviewed all octogenarians (n=38), who underwent lobectomy for stage I-II non-small-cell lung cancer (NSCLC) from 2000 to 2006. Inclusion criteria were: Tiffenau index<0.7, no adjuvant therapies, smoking cessation after surgery, spirometric data available after 12±3 months from surgery in the absence of relapsing disease. After excluding 14 patients (three died perioperatively), 24 fulfilled the inclusion criteria. The median preoperative forced expiratory volume in 1s (FEV1) was 80% (range 56.7-100%). The mean change in FEV1 after lobectomy resulted in a loss of 11% (range -32% to +7%, p=0.004). Considering two groups on the basis of median FEV1 (group 1: FEV1≤80%, group 2: FEV1>80%), mean FEV1 loss after surgery was 7.9% in group 1 and 14.9% in group 2, respectively (p=0.17). No statistical differences were found between the two groups in changes after surgery of forced vital capacity (FVC), arterial oxygen and carbon-dioxide tension. Diffusion capacity of the lung for carbon monoxide (DLCO)% loss was significantly higher in group 2 compared with group 1 (-22.5% vs +1.5%, p=0.001). Six patients showed an improvement of postoperative FEV1: all had a preoperative FEV1 less than 60%, an upper or homogeneous pattern of emphysema, and received an upper lobectomy. In group 2, the FEV1 loss was not affected by the type of lobectomy whereas in group 1, the resection of lower lobe was associated to a major FEV1 loss (-14.5% vs +5.3%, p=0.05). Octogenarians with lower preoperative FEV1% have a better late preservation of pulmonary function after lobectomy. Upper lobectomy seems to produce a lung-volume reduction effect, leading to an improvement in the expiratory volume in patients with higher airflow obstruction.

Comparative efficacy of once-daily ciclesonide and budesonide in the treatment of persistent asthma

The aim of this study was to compare the efficacy and safety of once-daily ciclesonide, a new-generation, on-site-activated, inhaled corticosteroid, with once-daily budesonide in persistent asthma. Eligible patients requiring budesonide or equivalent 320-640 microg (ex-mouthpiece, equivalent to 400-800 microg; Turbohalertrade mark) daily entered a 2-week baseline, and then a 2- to 4-week pretreatment period (budesonide 1280 microg/day; ex-mouthpiece, equivalent to 1600 microg/day). Patients with an increase in forced expiratory volume in 1s (FEV1) of 7% or 0.15 L were randomised to ciclesonide 320 microg (ex-actuator, equivalent to 400 microg ex-valve) via a hydrofluoroalkane-metered dose inhaler (HFA-MDI) without a spacer or budesonide 320 microg once daily in the morning for 12 weeks. Change in FEV1 was the primary endpoint. In all, 359 patients were randomised. The FEV1 and forced vital capacity (FVC) decreased by 0.18 and 0.12L, respectively, in the ciclesonide group, and by 0.23 and 0.21L in the budesonide group. For FEV1, ciclesonide was noninferior and numerically superior to budesonide. For FVC, ciclesonide was statistically superior to budesonide (P=0.010). Asthma symptom scores were comparable; the median percentage of symptom-free days was significantly higher for ciclesonide (43.6%) versus budesonide (25.8%) (P=0.017). Rescue medication use decreased significantly only for ciclesonide patients (P=0.009). Frequency of adverse events was low in both groups. Ciclesonide 320 microg once daily by HFA-MDI without a spacer was at least as effective as budesonide 320 microg once daily in persistent asthma.

Once versus three-times daily regimens of tobramycin treatment for pulmonary exacerbations of cystic fibrosis—the TOPIC study: a randomised controlled trial

Intravenous tobramycin (three-times daily) is widely used for pulmonary exacerbations in patients with cystic fibrosis who have chronic Pseudomonas aeruginosa infection. We undertook a double-blind, randomised controlled trial to assess the safety and efficacy of once versus three-times daily tobramycin in these patients. 244 patients from 21 cystic-fibrosis centres in the UK were randomly assigned to once or three-times daily tobramycin (with ceftazidime) for 14 days. Treatment was given as 30-min infusions of tobramycin in 0.9% saline. Primary outcome measure was change in forced expiratory volume in 1s (FEV1), over the 14 days of treatment, expressed as a percentage of the predicted normal value for age, sex, and height. We also measured the change in FEV1 expressed as a percentage of baseline. Secondary outcomes included change in serum creatinine. The study was powered for equivalence, and primary analysis was per protocol. 219 patients (107 once daily, 112 three-times daily) completed the study per protocol. None was lost to follow-up, although 20 discontinued intervention. Of 122 patients assigned to once daily treatment, three did not receive the study regimen. The mean change in FEV1 (% predicted) over 14 days was similar on the two regimens (10.4% [once daily] vs 10.0% [three-times daily]; adjusted mean difference 0.4% [95% CI -3.3 to 4.1]). Mean% change in FEV1 from baseline was also similar in both treatments (21.9% vs 22.1%; -0.1% [-8.0 to 7.9]). There was no significant difference in% change in creatinine from baseline (-1.5% [once daily] vs 1.7% [three-times daily]). However, in children, once daily treatment was significantly less nephrotoxic than was thrice daily (mean% change in creatine -4.5% [once daily] vs 3.7% [thrice daily]; adjusted mean difference -8.0%, 95% CI -15.7 to -0.4). No patients developed hearing loss during the study, although two reported acute dizziness and were withdrawn from the study. Intravenous tobramycin has equal efficacy if given once or three-times daily (with ceftazidime) for pulmonary exacerbations of cystic fibrosis. The once daily regimen might be less nephrotoxic in children.

Hypertonicity of the challenge solution may increase the diagnostic accuracy of histamine challenge

There is significant overlap in the responsiveness to direct airway challenges, such as the histamine challenge, between asthmatic and non-asthmatic subjects, which decreases their accuracy in the diagnosis of asthma. To minimise this overlap, a new test, hypertonic histamine challenge, was developed. Fifteen healthy subjects, 16 subjects with steroid-naive asthma, and 16 asthmatic subjects undergoing inhaled corticosteroid treatment underwent inhalation challenges with hypertonic saline, isotonic histamine, and hypertonic histamine, using an ultrasonic nebuliser and 2-min tidal breathing method. The increase in histamine solution tonicity decreased the histamine PC20 values only in the steroid-naive asthmatic subjects (1.1 (0.5-2.7) vs. 0.5 (0.2-1.2) mg/ml, P = 0.047). Using 1mg/ml as the cut-off value, the sensitivity, specificity, and accuracy of the hypertonic histamine challenge to detect steroid-naive asthma was 81%, 100%, and 90%. The respective values for the isotonic histamine challenge were 56%, 100%, and 77%. Furthermore, there was a statistically significant difference in the hypertonic histamine PC20 between steroid-naive and steroid-treated asthmatic subjects, which could not be detected in the isotonic histamine PC20. The hypertonic histamine PC20 was highly repeatable, with a single determination 95% range of +/-1.35 doubling concentrations. The hypertonic histamine challenge was safe but provoked more cough and throat irritation than the other two challenges. In conclusion, compared with a conventional, isotonic histamine challenge, hypertonic histamine challenge may be more accurate in the diagnosis of asthma and also, more capable to detect the effects of inhaled corticosteroid treatment.

Perception of bronchoconstriction in smokers with airflow limitation

To our knowledge, no data have been provided as to whether and to what extent dynamic hyperinflation, through its deleterious effect on inspiratory muscle function, affects the perception of dyspnoea during induced bronchoconstriction in patients with chronic airflow obstruction. We hypothesized that dynamic hyperinflation accounts in part for the variability in dyspnoea during acute bronchoconstriction. We therefore studied 39 consecutive clinically stable patients whose pulmonary function data were as follows (% of predicted value): vital capacity (VC), 97.8% (S.D. 16.0%); functional residual capacity, 105.0% (18.8%); actual forced expiratory volume in 1s (FEV1)/VC ratio, 56.1% (6.3%). Perception of dyspnoea using the Borg scale was assessed during a methacholine-induced fall in FEV1. The clinical score and the treatment score, the level of bronchial hyper-responsiveness and the cytological sputum differential count were also assessed. In each patient, the percentage fall in FEV1 and the concurrent Borg rating were linearly related, with the mean slope (PD slope) being 0.09 (0.06). The percentage fall in FEV1 accounted for between 41% and 94% of the variation in the Borg score. At a 20% fall in FEV1, the decrease in inspiratory capacity (ΔIC) was 0.156 (0.050) litres. Patients were divided into three subgroups according to the PD slope (arbitrary units/% fall in FEV1): subgroup I [eight hypoperceivers; PD slope 0.026 (0.005)], subgroup II [26 moderate perceivers; 0.090 (0.037)] and subgroup III [five hyperperceivers; 0.200 (0.044)]. By applying stepwise multiple regression analysis with the PD slope as the dependent variable, and other characteristics (demographic, clinical and functional characteristics, smoking history, level of bronchial hyper-responsiveness and sputum cytological profile) as independent variables, ΔIC (r2 = 45%, P &lt; 0.00001) and to a lesser extent treatment score (r2 = 17.3%, P &lt; 0.0006), and to an even lesser extent age (r2 = 3%, P &lt; 0.05), independently predicted a substantial amount (r2 = 65.27%, P &lt; 0.00001) of the variability in the Borg slope. Thus acute hyperinflation, and to a lesser extent treatment score and age, account in part for the variability in the perception of dyspnoea after accounting for changes in FEV1 during bronchoconstriction in patients with chronic airflow obstruction.

Primary ciliary dyskinesia: evolution of pulmonary function.

Pulmonary function tests were obtained in 11 patients with primary ciliary dyskinesia. Their mean age was 15 years (range 6-32). Their pulmonary function was obstructive, with a vital capacity (mean+/-SD) of 75%+/-20% predicted, a forced expiratory volume in 1s (FEV1) of 63%+/-20% predicted and a raised residual volume of 169%+/-50% predicted. After inhalation of 200 microg of salbutamol the mean change in FEV1 was + 13.2%+/-9.6% of the baseline value. In the 10 oldest patients, lung function had been measured at regular intervals during 3 20 years. Interestingly, during childhood and adolescence the evolution was not unfavourable: vital capacity increased by 8%+/-20% and FEV1 remained stable (mean change 0.3%+/-12%). Only 2 patients had an unfavourable evolution. At time of diagnosis, patients with primary ciliary dyskinesia have partially reversible obstructive airway disease. During regular follow up and therapy, there is no evidence of a further decline in lung function. Patients with associated immunodeficiency or important damage at the start of therapy may have a worse prognosis.