Moderate Airflow Obstruction Research Articles

A cluster analysis of chronic obstructive pulmonary disease in dusty areas cohort identified three subgroups

BackgroundChronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable clinical manifestations, structural changes, and treatment responses. In a cohort study, we performed a baseline cluster analysis to identify the subgroups of COPD and to assess the clinical outcomes of each subgroup during a 1-year follow-up.MethodsWe analyzed dusty areas cohort comprising 272 patients with COPD. The main factors with the highest loading in 15 variables were selected using principal component analysis (PCA) at baseline. The COPD patients were classified by hierarchical cluster analysis using clinical, physiological, and imaging data based on PCA-transformed data. The clinical parameters and outcomes during the 1-year follow-up were evaluated among the subgroups.ResultsPCA revealed that six independent components accounted for 77.3% of variance. Three distinct subgroups were identified through the cluster analysis. Subgroup 1 included younger subjects with fewer symptoms and mild airflow obstruction, and they had fewer exacerbations during the 1-year follow-up. Subgroup 2 comprised subjects with additional symptoms and moderate airflow obstruction, and they most frequently experienced exacerbations requiring hospitalization during the 1-year follow-up. Subgroup 3 included subjects with additional symptoms and mild airflow obstruction; this group had more female patients and a modest frequency of exacerbations requiring hospitalization.ConclusionsCluster analysis using the baseline data of a COPD cohort identified three distinct subgroups with different clinical parameters and outcomes. These findings suggest that the identified subgroups represent clinically meaningful subtypes of COPD.

Inhaled therapies in patients with moderate COPD in clinical practice: current thinking.

COPD is a complex, heterogeneous condition. Even in the early clinical stages, COPD carries a significant burden, with breathlessness frequently leading to a reduction in exercise capacity and changes that correlate with long-term patient outcomes and mortality. Implementation of an effective management strategy is required to reduce symptoms, preserve lung function, quality of life, and exercise capacity, and prevent exacerbations. However, current clinical practice frequently differs from published guidelines on the management of COPD. This review focuses on the current scientific evidence and expert opinion on the management of moderate COPD: the symptoms arising from moderate airflow obstruction and the burden these symptoms impose, how physical activity can improve disease outcomes, the benefits of dual bronchodilation in COPD, and the limited evidence for the benefits of inhaled corticosteroids in this disease. We emphasize the importance of maximizing bronchodilation in COPD with inhaled dual-bronchodilator treatment, enhancing patient-related outcomes, and enabling the withdrawal of inhaled corticosteroids in COPD in well-defined patient groups.

Diagnostic Instability and Reversals of Chronic Obstructive Pulmonary Disease Diagnosis in Individuals with Mild to Moderate Airflow Obstruction.

Chronic obstructive pulmonary disease (COPD) is a chronic, progressive disease, and reversal of COPD diagnosis is thought to be uncommon. To determine whether a spirometric diagnosis of mild or moderate COPD is subject to variability and potential error. We examined two prospective cohort studies that enrolled subjects with mild to moderate post-bronchodilator airflow obstruction. The Lung Health Study (n = 5,861 subjects; study duration, 5 yr) and the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study (n = 1,551 subjects; study duration, 4 yr) were examined to determine frequencies of (1) diagnostic instability, represented by how often patients initially met criteria for a spirometric diagnosis of COPD but then crossed the diagnostic threshold to normal and then crossed back to COPD over a series of annual visits, or vice versa; and (2) diagnostic reversals, defined as how often an individual's COPD diagnosis at the study outset reversed to normal by the end of the study. Diagnostic instability was common and occurred in 19.5% of the Lung Health Study subjects and 6.4% of the CanCOLD subjects. Diagnostic reversals of COPD from the beginning to the end of the study period occurred in 12.6% and 27.2% of subjects in the Lung Health Study and CanCOLD study, respectively. The risk of diagnostic instability was greatest for subjects whose baseline FEV1/FVC value was closest to the diagnostic threshold, and the risk of diagnostic reversal was greatest for subjects who quit smoking during the study. A single post-bronchodilator spirometric assessment may not be reliable for diagnosing COPD in patients with mild to moderate airflow obstruction at baseline.

White matter lesions characterise brain involvement in moderate to severe chronic obstructive pulmonary disease, but cerebral atrophy does not

BackgroundBrain pathology is relatively unexplored in chronic obstructive pulmonary disease (COPD). This study is a comprehensive investigation of grey matter (GM) and white matter (WM) changes and how these relate to disease severity and cognitive function.MethodsT1-weighted and fluid-attenuated inversion recovery images were acquired for 31 stable COPD patients (FEV1 52.1% pred., PaO2 10.1 kPa) and 24 age, gender-matched controls. T1-weighted images were segmented into GM, WM and cerebrospinal fluid (CSF) tissue classes using a semi-automated procedure optimised for use with this cohort. This procedure allows, cohort-specific anatomical features to be captured, white matter lesions (WMLs) to be identified and includes a tissue repair step to correct for misclassification caused by WMLs. Tissue volumes and cortical thickness were calculated from the resulting segmentations. Additionally, a fully-automated pipeline was used to calculate localised cortical surface and gyrification. WM and GM tissue volumes, the tissue volume ratio (indicator of atrophy), average cortical thickness, and the number, size, and volume of white matter lesions (WMLs) were analysed across the whole-brain and regionally – for each anatomical lobe and the deep-GM. The hippocampus was investigated as a region-of-interest. Localised (voxel-wise and vertex-wise) variations in cortical gyrification, GM density and cortical thickness, were also investigated. Statistical models controlling for age and gender were used to test for between-group differences and within-group correlations. Robust statistical approaches ensured the family-wise error rate was controlled in regional and local analyses.ResultsThere were no significant differences in global, regional, or local measures of GM between patients and controls, however, patients had an increased volume (p = 0.02) and size (p = 0.04) of WMLs. In patients, greater normalised hippocampal volume positively correlated with exacerbation frequency (p = 0.04), and greater WML volume was associated with worse episodic memory (p = 0.05). A negative relationship between WML and FEV1 % pred. approached significance (p = 0.06).ConclusionsThere was no evidence of cerebral atrophy within this cohort of stable COPD patients, with moderate airflow obstruction. However, there were indications of WM damage consistent with an ischaemic pathology. It cannot be concluded whether this represents a specific COPD, or smoking-related, effect.

Role of High-sensitivity C-reactive Protein as a Predictor of Severity of Chronic Obstructive Pulmonary Disease in Correlation with Clinical Parameters

ABSTRACTIntroductionChronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality throughout the world. By 2020, the World Health Organization predicts that COPD will become the third leading cause of death and the fifth leading cause of disability worldwide. The COPD is a complex disease characterized by slowly progressive and largely irreversible airflow obstruction due to chronic bronchitis and emphysema and associated with systemic inflammation.ObjectiveThis study aimed to correlate the plasma levels of high-sensitivity C-reactive protein (hs-CRP) with severity of COPD and pulmonary function tests [PFTs; according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages] and find out the relation between hs-CRP levels and clinical parameters of age, number of pack years, and body mass index (BMI) of the patient.Materials and methodsA cross-sectional study of 102 male patients with clinically and spirometrically diagnosed cases of COPD was performed. Data on patient's demographic characteristics, pack years, BMI, PFTs, and hs-CRP were analyzed.ResultsA total of 76 of the patients had moderate airflow obstruction (GOLD stages II and III), mild airflow obstruction was present in 14 patients (GOLD stage I), and 12 patients had severe airflow obstruction (GOLD stage IV). The hs-CRP was normal in 6 patients, while it was raised in 96 patients. The value of hs-CRP was correlated with age, pack years, BMI, and GOLD stages. There was a significant negative correlation between hs-CRP and BMI and a significant positive correlation between hs-CRP and age, pack years, and GOLD stages.ConclusionA raised level of CRP in COPD indicates reduced lung function; it plays an important role in systemic inflammation. This study supports the role of hs-CRP as a simple, cost-effective biochemical marker in the staging and determining the severity of COPD other than spirometry.How to cite this articlePatil MB, Abhishek M, Pradeep BK. Role of High-sensitivity C-reactive Protein as a Predictor of Severity of Chronic Obstructive Pulmonary Disease in Correlation with Clinical Parameters. J Med Sci 2017;3(2):50-54.

Effect of Fluticasone Furoate and Vilanterol on Exacerbations of Chronic Obstructive Pulmonary Disease in Patients with Moderate Airflow Obstruction

Inhaled corticosteroids have been shown to decrease exacerbations in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Their effects in patients with milder airflow obstruction remain unclear. This was an analysis of exacerbations in the SUMMIT (Study to Understand Mortality and Morbidity) study. In a double-blind, randomized controlled trial, once-daily inhaled placebo, fluticasone furoate (FF; 100 μg), vilanterol (VI; 25 μg), or the combination of FF/VI was administered. The primary outcome was all-cause mortality. Exacerbations of COPD were an additional predefined endpoint. A total of 1,368 centers in 43 countries and 16,485 patients with moderate COPD and heightened cardiovascular risk were included in the study. Compared with placebo, FF/VI reduced the rate of moderate and/or severe exacerbations by 29% (95% confidence interval [CI], 22-35; P < 0.001) and the rate of hospitalized exacerbations by 27% (95% CI, 13-39; P < 0.001). These relative effects were similar regardless of whether subjects had a history of exacerbation in the year before the study or an FEV1 <60% or ≥60% of predicted. The number needed to treat was not influenced by baseline FEV1 but was influenced by the history of exacerbations. FF/VI also reduced the rate of exacerbations treated with corticosteroids alone or with corticosteroids and antibiotics but not the rates of those treated with antibiotics alone. Patients with moderate chronic airflow obstruction experienced a reduction in exacerbations with FF/VI compared with placebo, irrespective of a history of exacerbations or baseline FEV1. Clinical trial registered with www.clinicaltrials.gov (NCT 01313676; GSK Study number 113782).

Determinants of Nicotine Dependence in Chronic Obstructive Pulmonary Disease.

BackgroundSmoking cessation is the most powerful intervention to modify progress of chronic obstructive pulmonary disease (COPD), and nicotine dependence is one of the most important determinants of success or failure in smoking cessation. We evaluated nicotine dependence status and investigated factors associated with moderate to high nicotine dependence in patients with COPD.MethodsWe included 53 current smokers with COPD in the Korean Obstructive Lung Disease II cohort enrolled between January 2014 and March 2016. Nicotine dependence was measured by using Fagerstrom test for nicotine dependence (FTND). Cognitive function was assessed by Korean version of Montreal Cognitive Assessment.ResultsThe median FTND score was 3, and 32 patients (60%) had moderate to high nicotine dependence. The median smoking amount was 44 pack-years, which was not related to nicotine dependence. Multiple logistic regression analysis revealed that high education status (odds ratio, 1.286; 95% confidence interval, 1.036–1.596; p=0.023), age <70 (odds ratio, 6.407; 95% confidence interval, 1.376–29.830; p=0.018), and mild to moderate airflow obstruction (odds ratio, 6.969; 95% confidence interval, 1.388–34.998; p=0.018) were related to moderate to high nicotine dependence.ConclusionNicotine dependence does not correlate with smoking amount, but with education level, age, and severity of airflow obstruction. Physicians should provide different strategies of smoking cessation intervention for current smokers with COPD according to their education levels, age, and severity of airflow obstruction.

Angiotensin-Converting Enzyme Inhibition as an Adjunct to Pulmonary Rehabilitation in Chronic Obstructive Pulmonary Disease.

Epidemiological studies in older individuals have found an association between the use of angiotensin-converting enzyme (ACE) inhibition (ACE-I) therapy and preserved locomotor muscle mass, strength, and walking speed. ACE-I therapy might therefore have a role in the context of pulmonary rehabilitation (PR). To investigate the hypothesis that enalapril, an ACE inhibitor, would augment the improvement in exercise capacity seen during PR. We performed a double-blind, placebo-controlled, parallel-group randomized controlled trial. Patients with chronic obstructive pulmonary disease, who had at least moderate airflow obstruction and were taking part in PR, were randomized to either 10 weeks of therapy with an ACE inhibitor (10 mg enalapril) or placebo. The primary outcome measurement was the change in peak power (assessed using cycle ergometry) from baseline. Eighty patients were enrolled, 78 were randomized (age 67 ± 8 years; FEV1 48 ± 21% predicted), and 65 completed the trial (34 on placebo, 31 on the ACE inhibitor). The ACE inhibitor-treated group demonstrated a significant reduction in systolic blood pressure (Δ, -16 mm Hg; 95% confidence interval [CI], -22 to -11) and serum ACE activity (Δ, -18 IU/L; 95% CI, -23 to -12) versus placebo (between-group differences, P < 0.0001). Peak power increased significantly more in the placebo group (placebo Δ, +9 W; 95% CI, 5 to 13 vs. ACE-I Δ, +1 W; 95% CI, -2 to 4; between-group difference, 8 W; 95% CI, 3 to 13; P = 0.001). There was no significant between-group difference in quadriceps strength or health-related quality of life. Use of the ACE inhibitor enalapril, together with a program of PR, in patients without an established indication for ACE-I, reduced the peak work rate response to exercise training in patients with chronic obstructive pulmonary disease.

Overview of Safety of Fluticasone Furoate, Vilanterol, or Their Combination in COPD Patients With Moderate Airflow Obstruction: The Summit Trial

Overview of Safety of Fluticasone Furoate, Vilanterol, or Their Combination in COPD Patients With Moderate Airflow Obstruction: The Summit Trial

Lung function and airway obstruction: associations with circulating markers of cardiac function and incident heart failure in older men—the British Regional Heart Study

AimsThe association between lung function and cardiac markers and heart failure (HF) has been little studied in the general older population. We have examined the association between lung function and...

Determinants of chronic obstructive pulmonary disease severity in the late-elderly differ from those in younger patients.

BackgroundAlthough the age range of chronic obstructive pulmonary disease (COPD) patients is broad, few studies have focused on the effects of age on disease characteristics.MethodsKeio University and affiliated hospitals established an observational COPD cohort. Patients were assessed using high resolution computed tomography (CT) to quantify emphysema, health status using the COPD assessment test (CAT) and the St. George’s Respiratory Questionnaire (SGRQ), spirometry, echocardiogram, dual X-ray absorption of bone, biomarkers and comorbid diagnoses. We examined the characteristics of COPD patients aged 75 and over compared with patients below 75.ResultsA total of 443 patients comprising 252 patients aged <75 years and 191 patients aged ≥75 years, were enrolled. Emphysematous changes on CT and prevalence of possible pulmonary hypertension were greater in late-elderly patients. The slope of the relationship between CT emphysema densitometry score and forced expiratory volume in 1 s was significantly less steep in the late-elderly than the younger patients (p = 0.002). CAT and total SGRQ scores and the frequency of long-term oxygen therapy were significantly higher in the late-elderly with moderate airflow obstruction compared to those of the younger in the same grade, although the opposite was seen in late-elderly patients with very severe airflow obstruction. Hypertension, aortic aneurysm, prostatic hypertrophy, anemia, and cataract are more prevalent in late-elderly patients.ConclusionsElderly COPD patients show a varied age-related pattern of disease that warrants specific attention in clinical practice above and beyond assessment of airflow limitation.Trial registration Clinical trial registered with the University Hospital Medical Information Network (UMIN000003470, April 10, 2010)Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-015-1810-8) contains supplementary material, which is available to authorized users.

Déficit en alpha-1 antitrypsine secondaire à une mutation Null

Alpha-1antitrypsin deficiency is a hereditary disease defined at the biological level by a serum alpha-1antitrypsin level below 11μM/L. The null variants are characterized by undetectable circulating alpha-1antitrypsin levels. Suspicion of a null variant requires the use of appropriate diagnostic techniques. We report the case of a 33-year old patient presenting with dyspnea on exertion, associated with a moderate airflow obstruction, incompletely reversible. His tobacco use was less than 3pack-years. The thoracic CT-scan showed emphysema. The serum alpha-1antitrypsin level was collapsed. Phenotyping by isoelectrofocusing on agarose gels did not show any band. The study of the SERPINA1gene, by PCR-sequence of the II, III, IV and V exons and the flanking intronic sequences, allowed identification of the NullQ0ourém allele in homozygous state. This mutation was found in heterozygous state in both parents of the index case and in one of his brothers. The index case showed a rapid aggravation of the airflow obstruction. In the case of a serum alpha-1antitrypsin deficiency, the analysis of the phenotype of the protein by isoelectrofocusing must be performed as a first-line investigation. The detection of an atypical profile may suggest the presence of deficient alleles other than the PI S and PI Z alleles that can only be characterized by sequencing of the whole SERPINA1gene. The patients carrying a null mutation have a high risk of severe chronic obstructive pulmonary disease.

Undiagnosed airflow limitation is common in patients with coronary artery disease and associated with cardiac stress

Smoking is a common risk factor for coronary artery disease (CAD) and chronic obstructive pulmonary disease (COPD). We evaluated the prevalence of undiagnosed COPD in patients with CAD and assessed the relationship between airflow obstruction and markers of cardiac stress. We recruited prospectively consecutive patients aged >40 years without known history of chronic lung disease (e.g. asthma, COPD, bronchiectasis) who had undergone percutaneous coronary intervention (PCI) for obstructive CAD between August 2009 and October 2010. Spirometry was performed and serum ST2, a novel biomarker of cardiomyocyte stress and fibrosis, was measured by enzyme-linked immunosorbent assay. Among 475 subjects (mean age 64 ± 9.7, range 42-85 years, 87.2% males, 58.5% current or ex-smokers) who underwent spirometry, 51 (10.7%) had undiagnosed airflow obstruction with FEV1 /FVC ratio <70%. Of these 51 subjects, 14 (2.9%), 23 (4.8%) and 14 (2.9%) had FEV1 ≥80, 50-80 and 30-50% predicted normal, respectively. ST2 level was measured in all the subjects with undiagnosed airflow obstruction and in 290 subjects with normal lung function. There was no significant difference in left ventricular ejection fraction on echocardiogram between subjects with and without airflow obstruction. Patients with severe airflow obstruction had a higher level of cardiac stress marker ST2 than those with mild and moderate airflow obstruction (rho = -0.214, P ≤ 0.001). Undiagnosed airflow obstruction is common among patients with CAD who have undergone PCI. Severity of airflow limitation is associated with increasing cardiac stress.

Implementation of a targeted screening program to detect airflow obstruction suggestive of chronic obstructive pulmonary disease within a presurgical screening clinic.

Targeted spirometry screening for chronic obstructive pulmonary disease (COPD) has been studied in primary care and community settings. Limitations regarding availability and quality of testing remain. A targeted spirometry screening program was implemented within a presurgical screening (PSS) clinic to detect undiagnosed airways disease and identify patients with COPD/asthma in need of treatment optimization. The present quality assurance study evaluated airflow obstruction detection rates and examined characteristics of patients identified through the targeted screening program. The targeted spirometry screening program was implemented within the PSS clinic of a tertiary care university hospital. Current or ex-smokers with respiratory symptoms and patients with a history of COPD or asthma underwent prebronchodilator spirometry. History of airways disease and smoking status were obtained during the PSS assessment and confirmed through chart reviews. After exclusions, the study sample included 449 current or ex-smokers. Abnormal spirometry results were found in 184 (41%) patients: 73 (16%) had mild, 93 (21%) had moderate and 18 (4%) had severe or very severe airflow obstruction. One hundred eighteen (26%) new cases of airflow obstruction suggestive of COPD were detected. One-half of these new cases had moderate or severe airflow obstruction. Only 34% of patients with abnormal spirometry results had reported a previous diagnosis of COPD. More than one-half of patients with abnormal spirometry results were current smokers. Undiagnosed airflow obstruction was detected in a significant number of smokers and ex-smokers through a targeted screening program within a PSS clinic. These patients can be referred for early intervention and secondary preventive strategies.

Influences of Chronic Obstructive Pulmonary Disease on Outcomes of Total Arch Replacement

Although an association between chronic obstructive pulmonary disease (COPD) and adverse surgical outcomes has been proposed, the impact of COPD severity on postoperative outcomes remains unclear. Our objective was to analyze the prognostic implication of COPD severity on outcomes after total aortic arch replacement. Between October 1999 and December 2012, 269 patients undergoing total arch replacement through median sternotomy, who were elective cases with preoperative spirometry records, were retrospectively reviewed. Patients were divided into four groups: control group, with ratio of forced expiratory volume of air in 1 second (FEV1) to forced vital capacity (FVC) of 70% or greater; mild airflow obstruction, with FEV1/FVC ratio less than 70% and FEV1 80% or greater of predicted; moderate airflow obstruction, FEV1/FVC ratio less than 70% and FEV1 50% to 79% of predicted; severe airflow obstruction, FEV1/FVC ratio less than 70% and FEV1 less than 50% of predicted. Symptoms of functional dyspnea and disability were also assessed. Multivariate logistic and Cox regression methods were used to determine if there was an independent association between COPD and short-term and long-term outcomes, respectively. The in-hospital mortality rate was 2.2% (6 of 269). A consistent trend of increasing frequency of postoperative respiratory complications with advanced airflow obstruction was noted. In multivariate analysis, in-hospital mortality (p = 0.022), incidence of respiratory complications (p = 0.021) and overall mortality (p = 0.025) was significantly associated with the symptoms of COPD, respectively. The severity of COPD as defined by spirometry and symptoms of functional dyspnea may be an important prognostic marker of patients undergoing total arch replacement.

Prevalence of Airflow Obstruction in U.S. Adults Aged 40–79 Years: NHANES Data 1988–1994 and 2007–2010

Background: The study evaluated the change in the prevalence of airflow obstruction in the U.S. population 40–79 years of age from years 1988–1994 to 2007–2010. Methods: Spirometry data from two representative samples of the U.S. population, the National Health and Nutrition Examination Surveys (NHANES) conducted in 1988–1994 and 2007–2010, were used. The American Thoracic Society/European Respiratory Society (ATS/ERS) criteria were used to define airflow obstruction. Results: Based on ATS/ERS criteria, the overall age-adjusted prevalence of airflow obstruction among adults aged 40–79 years decreased from 16.6% to 14.5% (p < 0.05). Significant decreases were observed for the older age category 60–69 years (20.2% vs. 15.4%; p < 0.01), for males (19.0% vs. 15.4%; p < 0.01), and for Mexican American adults (12.7% vs. 8.4%; p < 0.001). The prevalence of moderate and more severe airflow obstruction decreased also (6.4% vs. 4.4%; p < 0.01). Based on ATS/ERS criteria, during 2007–2010, an estimated 18.3 million U.S. adults 40–79 years had airflow obstruction, 5.6 million had moderate or severe airflow obstruction and 1.4 million had severe airflow obstruction. Conclusions: The overall age-adjusted prevalence of airflow obstruction among U.S. adults aged 40–79 years decreased from 1988–1994 to 2007–2010, especially among older adults, Mexican Americans, and males.

Disability and Recovery of Independent Function in Obstructive Lung Disease: The Cardiovascular Health Study

Background: Chronic obstructive lung disease frequently leads to disability. Older patients may experience transitions between states of disability and independence over time. Objective: To identify factors associated with transition between states of disability and independent function in obstructive lung disease. Methods: We analyzed data on 4,394 participants in the Cardiovascular Health Study who completed prebronchodilator spirometry. We calculated the 1-year probability of developing and resolving impairment in ≥1 instrumental activity of daily living (IADL) or ≥1 activity of daily living (ADL) using transition probability analysis. We identified factors associated with resolving disability using relative risk (RR) regression. Results: The prevalence of IADL impairment was higher with moderate (23.9%) and severe (36.9%) airflow obstruction compared to normal spirometry (22.5%; p < 0.001). Among participants with severe airflow obstruction, 23.5% recovered independence in IADLs and 40.5% recovered independence in ADLs. In the adjusted analyses, airflow obstruction predicted the development of IADL, but not ADL impairment. Participants with severe airflow obstruction were less likely to resolve IADL impairment [RR 0.67 and 95% confidence interval (CI) 0.49-0.94]. Compared to the most active individuals (i.e. who walked ≥28 blocks per week), walking less was associated with a decreased likelihood of resolving IADL impairment (7-27 blocks: RR 0.81 and 95% CI 0.69-0.86 and <7 blocks: RR 0.73 and 95% CI 0.61-0.86). Increased strength (RR 1.16 and 95% CI 1.05-1.29) was associated with resolving IADL impairment. Conclusions: Disability is common in older people, especially in those with severe airflow obstruction. Increased physical activity and muscle strength are associated with recovery. Research is needed on interventions to improve these factors among patients with obstructive lung disease and disability.

Efficacy of a physical exercise training programme COPD in primary care: study protocol of a randomized controlled trial.

BackgroundChronic obstructive pulmonary disease (COPD) is recognized as a systemic illness with significant extra-pulmonary features, such as exercise intolerance and muscle weakness. Pulmonary rehabilitation has been shown to be very effective in counteracting these consequences in patients with more advanced COPD. However, limited data is available on the efficacy of a physical exercise training programme in patients with mild to moderate COPD in primary care. Furthermore, it is unknown if improved exercise capacity translates into enhanced daily physical activities. The aim of this paper is to describe the design of a randomized controlled trial to assess the efficacy of a physical exercise training programme in patients with mild to moderate COPD.Methods/designIn this randomized controlled trial situated in the primary care setting, 102 patients with mild to moderate airflow obstruction (FEV1 ≥ 50% of predicted), dyspnoea and a physically inactive lifestyle will be randomized to an intervention or control group. The intervention group receives a 4-month physical exercise training programme at a local physiotherapy practice, which includes exercise training, resistance training, breathing exercises and advises on how to increase the level of physical activity. The control group receives usual care, i.e. advises on how to increase the level of physical activity and a sham treatment at a local physiotherapy practice of which no physiological training stimulus can be expected. Primary outcome is functional exercise capacity at 4-months measured on the six-minute walk distance. Secondary outcomes include peripheral muscle strength, physical activity in daily life, health related quality of life, Medical Research Council (MRC) dyspnoea score and patients’ perceived effectiveness. Follow-up measurement will take place at 6 months after baseline.DiscussionThis will be one of the first studies to evaluate the efficacy of a physical exercise training programme in patients with mild to moderate COPD completely recruited and assessed in primary care. The results of this trial may give a unique insight into the potential of the implementation of an easy, close-to-home rehabilitation programme.Trial registrationThe Netherlands National Trial Register NTR1471.

Chronic Productive Cough is Associated with Death in Smokers with Early COPD

Cough and phlegm are common in COPD. Previous studies have shown conflicting evidence regarding their association with mortality and lung function. We sought to better understand how cough and phlegm impact mortality and lung function in COPD. We analyzed data from the Lung Health Study, consisting of 5,887 smokers with mild to moderate airflow obstruction followed longitudinally. We assessed the association between baseline symptoms of cough alone, phlegm alone, and cough and phlegm with 12.5-year mortality and annual lung function decline. Average age at entry was 48.5 years (± 6.8) with 63% males and 4% African Americans. Cough alone was present in 17%, phlegm alone in 12%, while 31% had both. Neither symptom alone was associated with death, but the combination was associated with increased risk of death after adjustment for age, gender, race, smoking status at year 5, pack-years smoked, randomization group, baseline FEV1 percent predicted (HR 1.27, 95% CI 1.02–1.59). Individuals with cough and phlegm together more commonly died of respiratory causes than those without. Cough with phlegm was associated with 48 mL lower baseline FEV1 (95% CI –90, –6), while neither symptom alone was associated with baseline FEV1. No symptom was associated with FEV1 longitudinally. Cough and phlegm together are associated with mortality and lung function decrement in mild-to-moderate COPD, independent of lung function and smoking status. Respiratory causes of death are common among those with cough and phlegm. Such information can help to identify subsets of individuals with COPD having higher risk for adverse outcomes.

Omalizumab: clinical use for the treatment of an adolescent with difficult asthma

We describe the case of a 14 year old girl, followed by our Pediatric Allergology and Immunology Service for persistent rhinitis and asthma. The child suffered from asthma since the age of three years with a worsening of symptoms during the winter months. At 4 years of life, she was hospitalized for the first severe asthma episode. The SPT were positive for dust mites, Alternaria, pollens of grasses, Cypress, Birch, Plane, epithelium of dog and cat, fish and soy. She started a fish and soy free diet and therapy with ICS (50 mcg daily for 2), antihistamine and antileukotriene. At six years of life she performed spirometry, that showed moderate airflow obstruction (FEV1 75.8%) and significant dilatation after salbutamol (+16%). For persistence of asthma despite the therapy, at the age of 8 years she added LABA to the ICS (25/125 mcg daily for 2), with significant improvement for the next two years; spirometry normalized (FEV1 88.2%). When ten, she started with almost daily wheezing that required the use of OCS; spirometry showed severe bronchial obstruction and restriction (FEV1 58.8%). Chest X-ray was performed, showing peribronchial infiltration and air trapping; ph-metry, sweat test and Mantoux were negative; HRCT showed areas of thickening with appearance ground glass air trapping and bronchiectasis predominantly in the upper lobes. Immunological and autoimmune evaluation were negative. Monitoring with the Peak Flow Meter showed the persistence of frequent and severe symptoms; FEV1 was 48.5% with expansion of 28.6% after salbutamol. The girl was considered a candidate for therapy with omalizumab and this was started in Autumn 2011 (575 mg/2 weeks) with significant improvement (FEV1 100.5%). To date she is still treated with omalizumab, plus therapy with CSI + LABA, antileukotriene and antihistamine, with good control of asthma. On the basis of our experience, the use of omalizumab is an effective treatment for asthma resistant to common therapies, to reduce bronchial reactivity, symptoms and use of OCS.