Increased Lung Function Research Articles

Inhaled Steroids Modulate Extracellular Matrix Composition in Bronchial Biopsies of COPD Patients: A Randomized, Controlled Trial

RationaleSmoking and inflammation contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD), which involves changes in extracellular matrix. This is thought to contribute to airway remodeling and airflow obstruction. We have previously observed that long-term treatment with inhaled corticosteroids can not only reduce bronchial inflammation, but can also attenuate lung function decline in moderate-severe COPD. We hypothesized that inhaled corticosteroids and current smoking modulate bronchial extracellular matrix components in COPD.ObjectiveTo compare major extracellular matrix components (elastic fibers; proteoglycans [versican, decorin]; collagens type I and III) in bronchial biopsies 1) after 30-months inhaled steroids treatment or placebo; and 2) between current and ex-smokers with COPD.MethodsWe included 64 moderate-severe, steroid-naive COPD patients (24/40 (ex)-smokers, 62±7 years, 46 (31–54) packyears, post-bronchodilator forced expiratory volume in one second (FEV1) 62±9% predicted) at baseline in this randomized, controlled trial. 19 and 13 patients received 30-months treatment with fluticasone or placebo, respectively. Bronchial biopsies collected at baseline and after 30 months were studied using (immuno)histochemistry to evaluate extracellular matrix content. Percentage and density of stained area were calculated by digital image analysis.Results30-Months inhaled steroids increased the percentage stained area of versican (9.6% [CI 0.9 to 18.3%]; p = 0.03) and collagen III (20.6% [CI 3.8 to 37.4%]; p = 0.02) compared to placebo. Increased collagen I staining density correlated with increased post-bronchodilator FEV1 after inhaled steroids treatment (Rs = 0.45, p = 0.04). There were no differences between smokers and ex-smokers with COPD in percentages and densities for all extracellular matrix proteins.ConclusionsThese data show that long-term inhaled corticosteroids treatment partially changes the composition of extracellular matrix in moderate-severe COPD. This is associated with increased lung function, suggesting that long-term inhaled steroids modulate airway remodeling thereby potentially preventing airway collapse in COPD. Smoking status is not associated with bronchial extracellular matrix proteins.Trial RegistrationClinicalTrials.gov NCT00158847

Swimming training for asthma in children and adolescents aged 18 years and under

Asthma is the most common chronic medical condition in children and a common reason for hospitalisation. Observational studies have suggested that swimming, in particular, is an ideal form of physical activity to improve fitness and decrease the burden of disease in asthma. To determine the effectiveness and safety of swimming training as an intervention for asthma in children and adolescents aged 18 years and under. We searched the Cochrane Airways Group's Specialised Register of trials (CENTRAL), MEDLINE , EMBASE, CINAHL, in November 2011, and repeated the search of CENTRAL in July 2012. We also handsearchedongoing Clinical Trials Registers. We included all randomised controlled trials (RCTs) and quasi-RCTs of children and adolescents comparing swimming training with usual care, a non-physical activity, or physical activity other than swimming. We used standard methods specified in the Cochrane Handbook for Systematic reviews of Interventions. Two review authors used a standard template to independently assess trials for inclusion and extract data on study characteristics, risk of bias elements and outcomes. We contacted trial authors to request data if not published fully. When required, we calculated correlation coefficients from studies with full outcome data to impute standard deviation of changes from baseline. Eight studies involving 262 participants were included in the review. Participants had stable asthma, with severity ranging from mild to severe. All studies were randomised trials, three studies had high withdrawal rates. Participants were between five to 18 years of age, and in seven studies swimming training varied from 30 to 90 minutes, two to three times a week, over six to 12 weeks. The programme in one study gave 30 minutes training six times per week. The comparison was usual care in seven studies and golf in one study. Chlorination status of swimming pool was unknown for four studies. Two studies used non-chlorinated pools, one study used an indoor chlorinated pool and one study used a chlorinated but well-ventilated pool.No statistically significant effects were seen in studies comparing swimming training with usual care or another physical activity for the primary outcomes; quality of life, asthma control, asthma exacerbations or use of corticosteroids for asthma. Swimming training had a clinically meaningful effect on exercise capacity compared with usual care, measured as maximal oxygen consumption during a maximum effort exercise test (VO2 max) (two studies, n = 32), with a mean increase of 9.67 mL/kg/min; 95% confidence interval (CI) 5.84 to 13.51. A difference of equivalent magnitude was found when other measures of exercise capacity were also pooled (four studies, n = 74), giving a standardised mean difference (SMD) 1.34; 95% CI 0.82 to 1.86. Swimming training was associated with small increases in resting lung function parameters of varying statistical significance; mean difference (MD) for FEV1 % predicted 8.07; 95% CI 3.59 to 12.54. In sensitivity analyses, by risk of attrition bias or use of imputed standard deviations, there were no important changes on effect sizes. Unknown chlorination status of pools limited subgroup analyses.Based on limited data, there were no adverse effects on asthma control or occurrence of exacerbations. This review indicates that swimming training is well-tolerated in children and adolescents with stable asthma, and increases lung function (moderate strength evidence) and cardio-pulmonary fitness (high strength evidence). There was no evidence that swimming training caused adverse effects on asthma control in young people 18 years and under with stable asthma of any severity. However whether swimming is better than other forms of physical activity cannot be determined from this review. Further adequately powered trials with longer follow-up periods are needed to better assess the long-term benefits of swimming.

Intravenous antibiotics reduce the presence of Aspergillus in adult cystic fibrosis sputum

BackgroundPseudomonas aeruginosa and Aspergillus fumigatus frequently co-colonise the airways of patients with cystic fibrosis (CF). This study aimed to assess the impact of short-term administration of intravenous antipseudomonal antibiotics during...

La prise en charge de la crise d’asthme au service de pneumologie

Both smokers and patients with asthma can experience fixed airflow obstruction, which is associated with distinctive patterns of airway pathology. The influence of fixed airflow obstruction on the prognosis of these patients is unknown.We sought to investigate lung function decline and exacerbations in a 5-year prospective study of subjects with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease (COPD). We also sought to explore correlations between functional, pathological, and clinical features.Patients with fixed airflow obstruction due to asthma (n = 16) or COPD (n = 21) and a control group of asthmatic patients with fully reversible airflow obstruction (n = 15) were followed for 5 years.The rates of decline in FEV1 were similar in patients with fixed airflow obstruction caused by asthma (−49.7 ± 10.6 mL/y) or COPD (−51.4 ± 9.8 mL/y) and were higher than in asthmatic patients with reversible airflow obstruction (−18.1 ± 10.1 mL/y, P < .01). Exacerbation rates were also higher in patients with fixed airflow obstruction caused by asthma (1.41 ± 0.26 per patient-year) or COPD (1.98 ± 0.3 per patient-year) compared with those seen in asthmatic patients with reversible airflow obstruction (0.53 ± 0.11 per patient-year, P < .01). Baseline exhaled nitric oxide levels and sputum eosinophil counts correlated with the FEV1 decline in asthmatic patients with fixed airflow obstruction. By contrast, baseline sputum neutrophil counts, emphysema scores, comorbidities, and exacerbation frequency correlated directly and pulmonary diffusion capacity correlated inversely with the FEV1 decline in patients with COPD.In both patients with asthma and those with COPD, fixed airflow obstruction is associated with increased lung function decline and frequency of exacerbations. Nevertheless, the decline in lung function entails the specific pathological and clinical features of the underlying diseases.

Longitudinal decline in lung function in former asbestos exposed workers

BackgroundThis study was designed to assess the effect of asbestos exposure on longitudinal lung function decline.MethodsA group of 502 former asbestos-cement workers with at least two spirometry tests 4 years...

Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial

Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulatory properties. We tested the hypothesis that azithromycin would decrease the frequency of exacerbations, increase lung function, and improve health-related quality of life in patients with non-cystic fibrosis bronchiectasis. We undertook a randomised, double-blind, placebo-controlled trial at three centres in New Zealand. Between Feb 12, 2008, and Oct 15, 2009, we enrolled patients who were 18 years or older, had had at least one pulmonary exacerbation requiring antibiotic treatment in the past year, and had a diagnosis of bronchiectasis defined by high-resolution CT scan. We randomly assigned patients to receive 500 mg azithromycin or placebo three times a week for 6 months in a 1:1 ratio, with a permuted block size of six and sequential assignment stratified by centre. Participants, research assistants, and investigators were masked to treatment allocation. The coprimary endpoints were rate of event-based exacerbations in the 6-month treatment period, change in forced expiratory volume in 1 s (FEV(1)) before bronchodilation, and change in total score on St George's respiratory questionnaire (SGRQ). Analyses were by intention to treat. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12607000641493. 71 patients were in the azithromycin group and 70 in the placebo group. The rate of event-based exacerbations was 0·59 per patient in the azithromycin group and 1·57 per patient in the placebo group in the 6-month treatment period (rate ratio 0·38, 95% CI 0·26-0·54; p<0·0001). Prebronchodilator FEV(1) did not change from baseline in the azithromycin group and decreased by 0·04 L in the placebo group, but the difference was not significant (0·04 L, 95% CI -0·03 to 0·12; p=0·251). Additionally, change in SGRQ total score did not differ between the azithromycin (-5·17 units) and placebo groups (-1·92 units; difference -3·25, 95% CI -7·21 to 0·72; p=0·108). Azithromycin is a new option for prevention of exacerbations in patients with non-cystic fibrosis bronchiectasis with a history of at least one exacerbation in the past year. Health Research Council of New Zealand and Auckland District Health Board Charitable Trust.

Increased Lung Function Decline in Blue-collar Workers Exposed to Welding Fumes

There is no consensus at the present time about the effect of welding on lung function decline. This study compared lung function decline between blue-collar workers exposed and not exposed to welding fumes in a French longitudinal cohort of 21,238 subjects aged 37 to 52 years at inclusion. Medical data, occupation, sector of activity, and spirometry were recorded twice by occupational physicians in 1990 and 1995. A job-exposure matrix was used to identify 503 male blue-collar workers exposed to welding fumes and 709 control subjects and to define the weekly duration of exposure to welding fumes. Baseline lung function parameters were higher in workers exposed to welding fumes than in control subjects. After a 5-year follow-up, welding-fume exposure was associated with a nonsignificant decline in FVC (P = .06) and FEV(1) (P = .07) after adjustment for age, pack-years, BMI, and baseline value of the parameter. A significant accelerated decline in FEV(1) (P = .046) was also observed in never smokers exposed to welding fumes. An “exposure-response” relationship was observed between FEV(1) decline and weekly duration of exposure to welding fumes in nonsmokers but not in smokers. Blue-collar workers exposed to welding fumes showed accelerated decline in lung function, which, in nonsmokers, was related to weekly duration of exposure.

The Role of Pro-inflammatory and Anti-inflammatory Adipokines on Exercise-Induced Bronchospasm in Obese Adolescents Undergoing Treatment

Recent studies have demonstrated a greater prevalence in exercise-induced bronchospasm (EIB) in obese adolescents. However, the role of pro-/anti-inflammatory adipokines and the repercussions of obesity treatment on EIB need to be explored further. Therefore, the objective of this study was to evaluate the role of pro-/anti-inflammatory adipokines on EIB in obese adolescents evaluated after long-term interdisciplinary therapy. Thirty-five post-pubertal obese adolescents, including 20 non-EIB (body mass index [BMI] 36 ± 5 kg/m(2)) and 15 EIB (BMI 36 ± 5 kg/m(2)), were enrolled in this study. Body composition was measured by plethysmography, using the BOD POD body composition system, and visceral fat was analyzed by ultrasound. Serum levels of adiponectin and leptin were analyzed. EIB and lung function were evaluated according to the American Thoracic Society criteria. Patients were recruited to a 1-year interdisciplinary intervention of weight loss, consisting of medical, nutritional, exercise, and psychological components. Anthropometrics and lung function variables improved significantly after the therapy in both groups. Furthermore we observed a reduction in EIB occurrence in obese adolescents after treatment. There was an increase in adiponectin levels and a reduction in leptin levels after the therapy. In addition, a low FEV(1) value was a risk factor associated with EIB occurrence at baseline, and was correlated after treatment with changes in anthropometric and maximal O(2) consumption values as well as the adipokines profile. In the present study it was demonstrated that 1 year of interdisciplinary therapy decreased EIB frequency in obese adolescents, paralleled by an increase in lung function and improvement in pro-/anti-inflammatory adipokines.

Inhaled mannitol for the treatment of cystic fibrosis

Inhaled dry powder mannitol is well established for use in bronchial provocation testing. Inhaled mannitol also increases mucociliary clearance, and therefore could have a role in treating chronic suppurative lung disease. There have been a number of studies in cystic fibrosis and bronchiectasis. An international Phase III trial has just been published that suggests the use of regular inhaled mannitol increases lung function and reduces exacerbation frequency in cystic fibrosis. Inhaled mannitol exerts its effects in a number of ways, most importantly like hypertonic saline, setting up an osmotic gradient so water flows into the airway lumen, increasing mucus hydration and mucociliary clearance. Its formulation as a dry powder makes it quick and convenient to take.

Exercise improves lung function and habitual activity in children with cystic fibrosis

BackgroundCystic fibrosis (CF) lung disease leads to progressive deterioration in exercise capacity. Because physical activity has been shown to improve lung function and quality of life (QoL), developing routine exercise programs can benefit this patient population. MethodsLung function, nutritional status, and exercise capacity and assessments of habitual activity and QoL were measured before and after a two-month, subject-designed exercise regimen based on self-reported activity assessment. Statistical analysis included Wilcoxon signed-rank, Wilcoxon rank sum, and Fisher's exact tests. ResultsSubjects completing the study demonstrated significant improvement in exercise capacity and body image perception, a CF-specific QoL measure (p<0.001). In secondary analyses, subjects improving exercise capacity showed significant increases in lung function and self-reported habitual activity. ConclusionsIncreases in exercise capacity over a two-month period resulted in significantly improved lung function and self-reported habitual activity. Longer, controlled trials are needed to develop individualized exercise recommendations.

Breastfeeding is associated with increased lung function at 18 years of age: a cohort study

Breastfeeding has been linked with increased forced vital capacity (FVC) in children but not in older adolescents. Our aim was to investigate the effects of breastfeeding duration and infant weight gain on FVC in both developmental periods. In a birth cohort, information on breastfeeding duration was collected at 1 and 2 yrs; spirometric tests were conducted at 10 and 18 yrs. To estimate the effect of breastfeeding duration on FVC at 18 yrs of age, we used linear models; to analyse repeated FVC measurements at 10 and 18 yrs of age, we used linear mixed models. Links between breastfeeding, infant weight gain and FVC at 10 and 18 yrs of age were analysed through path analyses. Among 808 breastfed children, 49% were breastfed for ≥ 4 months. At 18 yrs of age the augmenting effect of breastfeeding on FVC was reduced with increased height. Linear mixed models identified that breastfeeding duration was associated with increased FVC. Path analysis suggested a direct effect of breastfeeding on FVC at 10 yrs of age, but an indirect effect at 18 yrs of age via FVC at 10 yrs of age. Although inversely related to breastfeeding, a higher weight gain in infants led to taller adolescents and, in turn, resulted in increased FVC. In conclusion, a longer duration of breastfeeding contributes to lung health in childhood and adolescence.

Asthma outcome measures

Asthma is a common chronic disease with underlying inflammation of the airway. Advances in science have led to increased understanding of the heterogeneous nature of asthma and its complex mechanisms. Traditionally, asthma-practice guidelines have focused on optimizing lung function and the US FDA has required increases in lung function and reduction of exacerbation as primary outcomes in clinical trials of new asthma therapeutics. Improved lung function is a critical indicator of bronchodilator therapy, but the importance of long-term asthma control while maintained on controller medication is increasingly emphasized. The NIH asthma guidelines suggest the use of patient-reported outcomes, including health-related quality-of-life measures, to assess asthma control. Clinical practices and research studies concerning asthma can benefit from harmonizing the major outcome measures so that comparisons across studies can be made. In this article, we review common asthma outcome measures with a focus on recent efforts to harmonize outcomes for therapeutic clinical trials in asthma.

Choice of Bronchodilator Therapy for Patients with COPD

Chronic obstructive pulmonary disease (COPD) is a progressive airway inflammatory condition that is associated with accelerated decline of lung function and is characterized by worsening dyspnea with episodes of increased number and severity of symptoms, termed exacerbations.1 The main objectives of managing COPD are a reduction in the severity of symptoms and the prevention of exacerbations.2 Bronchodilator therapy is central to the management of COPD; this treatment produces modest increases in lung function as measured by spirometry and a reduction in the dynamic hyperinflation that leads to the dyspnea of COPD.3 Patients with COPD often present to their physician with . . .

Lung function decline in relation to mould and dampness in the home: the longitudinal European Community Respiratory Health Survey ECRHS II

BackgroundThere are few longitudinal studies that have examined the association of lung function decline with indoor mould and dampness. Lung function decline in relation to dampness and mould in the...

Swimming Pool Attendance, Asthma, Allergies, and Lung Function in the Avon Longitudinal Study of Parents and Children Cohort

Cross-sectional studies have reported inconsistent findings for the association between recreational swimming pool attendance and asthma and allergic diseases in childhood. To examine whether swimming in infancy and childhood was associated with asthma and allergic symptoms at age 7 and 10 years in a UK longitudinal population-based birth cohort, the Avon Longitudinal Study of Parents and Children. Data on swimming were collected by questionnaire at 6, 18, 38, 42, 57, 65, and 81 months. Data on rhinitis, wheezing, asthma, eczema, hay fever, asthma medication, and potential confounders were collected through questionnaires at 7 and 10 years. Spirometry and skin prick testing were performed at 7 to 8 years. Data for analysis were available for 5,738 children. At age 7 years, more than 50% of the children swam once per week or more. Swimming frequency did not increase the risk of any evaluated symptom, either overall or in atopic children. Children with a high versus low cumulative swimming pool attendance from birth to 7 years had an odds ratio of 0.88 (95% confidence interval, 0.56-1.38) and 0.50 (0.28-0.87), respectively, for ever and current asthma at 7 years, and a 0.20 (0.02-0.39) standard deviation increase in the forced midexpiratory flow. Children with asthma with a high versus low cumulative swimming had an odds ratio for current asthma at 10 years of 0.34 (0.14-0.80). This first prospective longitudinal study suggests that swimming did not increase the risk of asthma or allergic symptoms in British children. Swimming was associated with increased lung function and lower risk of asthma symptoms, especially among children with preexisting respiratory conditions.

Lung Development, Lung Function, and Retinoids

In this issue of the Journal, Checkley et al. report that, in a region with endemic vitamin A (retinol) deficiency, children whose mothers had received vitamin A supplementation before, during, and for 6 months after pregnancy had better lung function when they were tested at 9 to 11 years of age than children whose mothers had received beta carotene supplementation or placebo.1 The extent of the increased lung function was linearly related to the mother's postpartum serum retinol concentration. Because of a local ordinance, all children received supplemental vitamin A beginning at 6 months of age.1 Thus, the period during . . .

Fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease: 5-year follow-up

Both smokers and patients with asthma can experience fixed airflow obstruction, which is associated with distinctive patterns of airway pathology. The influence of fixed airflow obstruction on the prognosis of these patients is unknown. We sought to investigate lung function decline and exacerbations in a 5-year prospective study of subjects with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease (COPD). We also sought to explore correlations between functional, pathological, and clinical features. Patients with fixed airflow obstruction due to asthma (n = 16) or COPD (n = 21) and a control group of asthmatic patients with fully reversible airflow obstruction (n = 15) were followed for 5 years. The rates of decline in FEV(1) were similar in patients with fixed airflow obstruction caused by asthma (-49.7 +/- 10.6 mL/y) or COPD (-51.4 +/- 9.8 mL/y) and were higher than in asthmatic patients with reversible airflow obstruction (-18.1 +/- 10.1 mL/y, P < .01). Exacerbation rates were also higher in patients with fixed airflow obstruction caused by asthma (1.41 +/- 0.26 per patient-year) or COPD (1.98 +/- 0.3 per patient-year) compared with those seen in asthmatic patients with reversible airflow obstruction (0.53 +/- 0.11 per patient-year, P < .01). Baseline exhaled nitric oxide levels and sputum eosinophil counts correlated with the FEV(1) decline in asthmatic patients with fixed airflow obstruction. By contrast, baseline sputum neutrophil counts, emphysema scores, comorbidities, and exacerbation frequency correlated directly and pulmonary diffusion capacity correlated inversely with the FEV(1) decline in patients with COPD. In both patients with asthma and those with COPD, fixed airflow obstruction is associated with increased lung function decline and frequency of exacerbations. Nevertheless, the decline in lung function entails the specific pathological and clinical features of the underlying diseases.

Socioeconomic risk factors for lung function decline in a general population

The aim of our study was to examine sex-specific associations between different aspects of socioeconomic status (SES) (educational level, occupational status, income) and lung function in a general adult population. In the Hordaland County Cohort Study, 1,644 subjects aged 26-82 yrs at baseline answered questionnaires and performed post-bronchodilator spirometry both in 1996-1997 and in 2003-2006. We performed adjusted linear regression analysis on the effect of SES on decline in forced experimental volume in 1 s (FEV(1)), forced vital capacity (FVC) and FEV(1)/FVC. Mean annual decline in FEV(1) from baseline to follow-up was 57 mL (se 1.3) and 48 mL (se 1.0) for males and females, respectively. Males had a larger decline in FVC than females, while females had a larger decline in FEV(1)/FVC. Lower education and low occupational status were associated with larger male lung function decline. SES did not affect female lung function decline. However, marital status was a significant predictor; unmarried females had less decline than both married and widowed females in both FEV(1) (adjusted mean annual difference 8 mL and 16 mL) and FVC (adjusted mean annual difference 8 mL and 18 mL). Low SES was associated with increased lung function decline in males. For females, marital status was more important.

Chronic Mycobacterium abscessus infection and lung function decline in cystic fibrosis

Background Although nontuberculous mycobacteria (NTM) are recognized pathogens in cystic fibrosis (CF), associations with clinical outcomes remain unclear. Methods Microbiological data was obtained from 1216 CF patients over 8 years (481 ± 55 patients/year). Relationships to clinical outcomes were examined in the subset ( n = 271, 203 ± 23 patients/year) with longitudinal data. Results Five hundred thirty-six of 4862 (11%) acid-fast bacilli (AFB) cultures grew NTM, with Mycobacterium abscessus ( n = 298, 55.6%) and Mycobacterium avium complex ( n = 190, 35.4%) most common. Associated bacterial cultures grew Stenotrophomonas or Aspergillus species more often when NTM were isolated (18.2% vs. 8.4% and 13.9% vs. 7.2%, respectively, p < 0.01). After controlling for confounders, patients with chronic M. abscessus infection had greater rates of lung function decline than those with no NTM infection (− 2.52 vs. − 1.64% predicted FEV 1/year, p < 0.05). Conclusions NTM infection is common in CF and associated with particular pathogens. Chronic M. abscessus infection is associated with increased lung function decline.

Management of Chronic Obstructive Pulmonary Disease with Tiotropium Bromide

In COPD, pathologic upregulation and stimulation of muscarinic (M) receptors contribute to bronchospasm, mucus hypersecretion and possibly airway remodeling. Tiotropium bromide (brand name Spiriva; Boehringer Ingelheim/Pfizer) inhalational powder was approved by the US Food and Drug Administration in January 2004 for the long-term, once-daily, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. Tiotropium is recommended by the Global initiative for Chronic Obstructive Lung Disease (GOLD) as a first-line therapeutic in treating chronic moderate and severe COPD and is the only long acting inhaled anti-muscarinic (anti-cholinergic) therapy available for the treatment of COPD in the USA. The primary functional effect of tiotropium is mediated through antagonism of M3 receptors and the decreased acetylcholine induced airway smooth muscle bronchoconstriction. Tiotropium is associated with increased lung function, health related quality of life, and exercise tolerance and reduced dyspnea and acute exacerbations of COPD (AECOPD). On November 19, 2009 the Pulmonary-Allergy Drugs Advisory Committee voted 11-1 for new product labeling about the benefits of tiotropium stating that the data provide “substantial and convincing evidence” that tiotropium decreases AECOPD. 1 This indication “for reducing COPD exacerbations” was added to product labeling in December 2009. Tiotropium is safe and well tolerated with few side effects. The large multicenter UPLIFT (Understanding the Potential Long-Term Impacts on Function with Tiotropium) trial demonstrated the long-term safety of tiotropium over four years of continuous use showing no increase in stoke and all cause mortality. Serious adverse events including respiratory failure, congestive heart failure and myocardial infarction were significantly less in the tiotropium group. In a pre-specified subgroup analysis Tiotropium retarded FEV1 decline in milder COPD. Additional review of cholinergic pathobiology relevant to COPD and asthma provides context for future therapeutic and preventative roles for tiotropium.