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Multi-trait polygenic scores for COPD and COPD exacerbations implicate druggable proteins.

BACKGROUNDWe constructed multi-trait polygenic risk scores (PRSs) predicting chronic obstructive pulmonary disease (COPD) and exacerbations, validated their performance in diverse cohorts, and identified PRS-related proteins for potential therapeutic targeting.METHODSPRSmix+, a multi-trait PRS framework, is used to train a composite PRS (PRSmulti) in COPDGene non-Hispanic White participants (n = 6,647). Associations of PRSmulti with COPD status (GOLD 2-4 vs. GOLD 0 or ICD) and exacerbation frequency were tested in COPDGene African American (n = 2,466), ECLIPSE (n = 1,858), Mass General Brigham Biobank (n = 15,152), and All of Us (n = 118,566). Protein prediction models were applied to GWAS summary statistics from traits contributing to PRSmulti and were validated with proteomic data in COPDGene (n = 5,173) and UK Biobank (n = 5,012).RESULTSPRSmix+ selected 7 traits for PRSmulti. In multivariable models, PRSmulti was associated with COPD status (meta-analysis random effects [RE] OR 1.58 [95% CI: 1.28-1.94]) and exacerbation frequency (meta-analysis RE β 0.21 [95% CI: 0.11-0.31]), with higher effect sizes observed in smoking-enriched cohorts. PRSmulti outperformed traditional single-trait PRS in all tested cohorts. Using protein prediction models, we identified 73 proteins associated with the PRSs that were also validated with measured protein levels in COPDGene and UK Biobank. Of these proteins, 25 were linked to approved or investigational drugs. Notable targets include RAGE/sRAGE, IL1RL1, and SCARF2, all implicated in COPD pathogenesis and exacerbations.CONCLUSIONSMulti-trait PRS improves prediction of COPD and exacerbation risk. Integration with proteomic data identifies druggable protein targets, offering a promising avenue for precision medicine in COPD management.TRIAL REGISTRATIONCOPDGene: ClinicalTrials.gov NCT00608764; ECLIPSE: ClinicalTrials.gov NCT00292552.

Humans↗

How well do we care for patients with end stage chronic obstructive pulmonary disease (COPD)? A comparison of palliative care and quality of life in COPD and lung cancer.

BACKGROUND: Patients with severe chronic obstructive pulmonary disease (COPD) have a poor quality of life and limited life expectancy. This study examined whether these patients were relatively disadvantaged in terms of medical and social care compared with a group with inoperable lung cancer. METHODS: An open two group comparison was made of 50 patients with severe COPD (forced expiratory volume in one second (FEV(1)) <0.75 l and at least one admission for hypercapnic respiratory failure) and 50 patients with unresectable non-small cell lung cancer (NSCLC). A multi-method design was used involving standardised quality of life tools, semi-structured interviews, and review of documentation. RESULTS: The patients with COPD had significantly worse activities of daily living and physical, social, and emotional functioning than the patients with NSCLC (p<0.05). The Hospital Anxiety and Depression Scale (HADS) scores suggested that 90% of patients with COPD suffered clinically relevant anxiety or depression compared with 52% of patients with NSCLC. Patients were generally satisfied with the medical care received, but only 4% in each group were formally assessed or treated for mental health problems. With regard to social support, the main difference between the groups was that, while 30% of patients with NSCLC received help from specialist palliative care services, none of the patients with COPD had access to a similar system of specialist care. Finally, patients in both groups reported a lack of information from professionals regarding diagnosis, prognosis and social support, although patients' information needs were disparate and often conflicting. CONCLUSION: This study suggests that patients with end stage COPD have significantly impaired quality of life and emotional well being which may not be as well met as those of patients with lung cancer, nor do they receive holistic care appropriate to their needs.

Aged↗

Impact of COPD in North America and Europe in 2000: subjects' perspective of Confronting COPD International Survey.

To date, no international surveys estimating the burden of chronic obstructive pulmonary disease (COPD) in the general population have been published. The Confronting COPD International Survey aimed to quantify morbidity and burden in COPD subjects in 2000. From a total of 201,921 households screened by random-digit dialling in the USA, Canada, France, Italy, Germany, The Netherlands, Spain and the UK, 3,265 subjects with a diagnosis of COPD, chronic bronchitis or emphysema, or with symptoms of chronic bronchitis, were identified. The mean age of the subjects was 63.3 yrs and 44.2% were female. Subjects with COPD in North America and Europe appear to underestimate their morbidity, as shown by the high proportion of subjects with limitations to their basic daily life activities, frequent work loss (45.3% of COPD subjects of <65 yrs reported work loss in the past year) and frequent use of health services (13.8% of subjects required emergency care in the last year), and may be undertreated. There was a significant disparity between subjects' perception of disease severity and the degree of severity indicated by an objective breathlessness scale. Of those with the most severe breathlessness (too breathless to leave the house), 35.8% described their condition as mild or moderate, as did 60.3% of those with the next most severe degree of breathlessness (breathless after walking a few minutes on level ground). This international survey confirmed the great burden to society and high individual morbidity associated with chronic obstructive pulmonary disease in subjects in North America and Europe.

Age Distribution↗

Compliance during long-term treatment with fluticasone propionate in subjects with early signs of asthma or chronic obstructive pulmonary disease (COPD): results of the Detection, Intervention, and Monitoring Program of COPD and Asthma (DIMCA) Study.

In a prospective study, we investigated the long-term compliance to fluticasone propionate (FP) by dry powder inhalation (Rotadisk) in subjects with early signs of asthma and chronic obstructive pulmonary disease (COPD) without an established diagnosis. Subjects were selected from a large screening program on early stages of asthma and COPD (Detection, Intervention, and Monitoring Program of COPD and Asthma [DIMCA] program) in the general practice. Forty-eight adult subjects with "early signs of COPD" (slightly increased forced expiratory volume in 1 sec [FEV1] decline of >0.04L/year) and 29 adult subjects with "early signs of asthma" (signs of bronchial hyperresponsiveness or reversibility) participated in a randomized placebo-controlled trial with FP (Flixotide 500 microg daily) versus placebo with a duration of 2 years or 1 year, respectively. Compliance was measured by counting Rotadisks returned. By means of a questionnaire, participants were asked about perceived effects and/or side effects of the trial drug. The mean overall individual compliance rates of 72% (range 7%-102%) in the early COPD trial and 71% (range 8%-99%) in the early asthma trial were maintained throughout the study. Perceived effectiveness (12% of the participants) or side effects (30% of the participants) of the trial drug were not related to compliance. The willingness of patients to use the trial drug in daily practice if efficacy would be proved was statistically significantly related to compliance during the trial (p = 0.017). It was concluded that the compliance rates found were relatively high in patients with symptoms of mild asthma or COPD without an established diagnosis. Conviction of the importance of treatment influenced compliance more positively than perceived (side) effects. These results again emphasize the importance of patient education in establishing early treatment with inhaled corticosteroids.

Administration, Inhalation↗

Combination therapy in COPD: different response of COPD stages and predictivity of functional parameters.

BACKGROUND: Inhaled corticosteroids reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD) but they do not affect disease progression. FEV1, as single parameter, showed limits in describing the heterogeneity of COPD population. Combination therapy, with long-acting Beta2-agonist and corticosteroid, showed a more beneficial effect on lung function, exacerbations, and health status than single inhaled drug. The aim of this study was to assess, in stable COPD, which stage (mild, moderate, severe) shows the best response after 12 weeks inhaled treatment, and which starting functional parameters show a correlation with the response. METHODS: 170 stable COPD patients (38 mild, 66 moderate, 66 severe) were enrolled. Patients received salmeterol/fluticasone 50/500 microg Metered Dose Inhaler (MDI) bid for 12 weeks. Pulmonary function tests and clinical data were performed. Results were subdivided, on functional and clinical data, in "responders (R)" and "no-responders (NR)". RESULTS: A FEV1 improvement (+ 12% and 200 ml) was achieved in 21 mild, 28 moderate and 17 severe COPD patients, respectively 55.3%, 45.9%, and 30.9% of each group. Statistical analysis of starting functional parameters showed a correlation with the therapeutic response for FEV1/FVC, MEF50 and DLCO/VA% (p < 0.05). CONCLUSIONS: Salmeterol/fluticasone improves FEV1% in mild and moderate more than in severe COPD patients. The study confirmed the difference in response between early and advanced stage. Starting FEV1/FVC and MEF50 were significant predictors in mild and moderate stages, and starting DLCO/VA% resulted a significant predictor in moderate and severe stages.

Administration, Inhalation↗

The diagnostic accuracies of chronic obstructive pulmonary disease (COPD) in general practice: The results of the MAGIC (Manchester Airways Group Identifying COPD) study.

BACKGROUND: Although it is generally accepted that chronic obstructive pulmonary disease (COPD) is underdiagnosed, there is little objective information concerning the size of the problem in the UK. METHOD: Patients from two general practices were offered spirometry if they were aged 30 or older, had reported ever smoking in one of four postal respiratory surveys (1993-2001), and/or reported four or more symptoms or risk factors in 2001 indicating likely obstructive airways disease. RESULTS: Of 2646 subjects invited, 871 attended and 825 had adequate spirometry results for analysis. In all, 163 patients had spirometrically-confirmed COPD; 103 of these (63.2%) had no recorded COPD in their practice records, including 14 out of 31 (45.2%) whose spirometry results classified them as having severe or very severe COPD. CONCLUSION: This study found a considerable under-recording of COPD in two general practices. This may be due to a combination of administrative and diagnostic problems (including the under-use of spirometers), and a reluctance of patients to present with their symptoms. These results have important implications in terms of unmet need and resource utilisation.

Adult↗

COPD in Japan: the Nippon COPD Epidemiology study.

OBJECTIVES: Despite high smoking rates, few prevalence studies of COPD have been performed in Asia. The Nippon COPD Epidemiology (NICE) Study used spirometry to measure prevalence of airflow limitation in Japanese adults. METHODOLOGY: Clinical, spirometric, and risk factor exposure data were collected on 2343 subjects aged > or = 40 years who were demographically similar to the Japanese population. Airflow limitation was defined according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (FEV1/FVC < 70%). RESULTS: Prevalence of airflow limitation was 10.9%. Based upon GOLD severity criteria, 56% of these cases were found to be mild, 38% moderate, 5% severe, and 1% very severe. Airflow limitation was significantly more prevalent in males than females (16.4% vs. 5.0%; P < 0.001), in male ever-smokers than female ever-smokers (17.1% vs. 7.5%; P < 0.001), and in older subjects (3.5% in 40-49 years olds vs. 24.4% in those > 70 years; P < 0.001). Of note, airflow limitation was also found in 5.8% of non-smokers and 4.6% of those younger than age 60 years. Only 9.4% of cases with airflow limitation reported a previous diagnosis of COPD. CONCLUSIONS: Prevalence of airflow limitation in Japan is higher than previously reported, suggesting a high degree of under-recognition of COPD. The high prevalence of smoking coupled with an aging population threatens to further increase the burden of COPD, highlighting the need for enhanced screening efforts and interventions of prevention and treatment.

Adult↗

Trends in the epidemiology of COPD in Canada, 1980 to 1995. COPD and Rehabilitation Committee of the Canadian Thoracic Society.

PURPOSE: To describe trends in the epidemiology of COPD in Canada from 1980 to 1995, in terms of perceived prevalence, mortality, and hospital morbidity. DATA SOURCES: We limited the analysis to data related to chronic bronchitis, emphysema, or chronic airway obstruction not classified elsewhere, and excluded asthma (Ninth International Classification of Diseases, codes 490 to 492 and 496). The perceived prevalence rate of COPD was derived from the 1994-1995 National Health Survey. Mortality and hospital morbidity data (from 1980 to 1995) were obtained from the Health Statistics Division of Statistics Canada. RESULTS: From the National Health Survey, it was estimated that 750,000 Canadians had chronic bronchitis or emphysema diagnosed by a health professional. Prevalence rates were the following: ages 55 to 64 years, 4.6%; ages 65 to 74 years, 5.0%; > or =75 years, 6.8%. From 1980 to 1995, the total number of deaths from COPD increased from 4,438 to 8,583. Although the age-standardized mortality rate remained stable throughout this period in men (around 45/100,000 population), it doubled in women (8.3/100,000 in 1980 to 17.3/100,000 in 1995). There were 55,782 hospital separations in 1993-1994 with COPD as the primary discharge diagnosis (compared to 42,102 in 1981-1982). In people aged > or =65 years, the age-specific hospital separation rate increased over this period, especially in women > or =75 years (from 504/100,000 to 1,033/100,000). The average in-hospital length of stay was 9.6 days in 1981-1982 and 8.3 days in 1993-1994. CONCLUSION: COPD represents a major health issue in Canada and will likely remain so for decades. Physician and non-physician health professionals who provide health care, as well as those who fund it must actively encourage approaches for primary and secondary prevention of this condition as well as approaches shown to be effective in addressing its associated impairment, disability, and handicap.

Aged↗

Hypercapnic-hypoxemic chronic obstructive pulmonary disease (COPD): influence of severity of COPD on nutritional status.

In 90 patients with hypercapnic-hypoxemic chronic obstructive pulmonary disease (COPD), noninvasive anthropometric and biochemical nutritional indices were measured to assess the prevalence and features of malnutrition in COPD and to analyze the relationship between nutritional depletion and the severity of the disease. A significant inverse relationship was found between PaCO2 and body weight; a parallel decrease of both somatic proteins and body-energy stores of fat appears to be paired with decreasing body weight. Deterioration of nutritional status occurred in the COPD patients considered despite seemingly adequate calorie and protein intakes, although in patients with more severe impairment of pulmonary gas exchange, calorie intake was significantly lower compared with basal energy expenditure. In the course of hypercapnic-hypoxemic COPD malnutrition is common, it is related to the severity of the disease as judged by the need for hospitalization and degree of impairment of gas exchange, and it may be present despite apparently adequate nutrient intake.

Aged↗

UK National COPD Audit 2003: Impact of hospital resources and organisation of care on patient outcome following admission for acute COPD exacerbation.

BACKGROUND: Acute chronic obstructive pulmonary disease (COPD) exacerbations use many hospital bed days and have a high rate of mortality. Previous audits have shown wide variability in the length of stay and mortality between units not explained by patient factors. This study aimed to explore associations between resources and organisation of care and patient outcomes. METHODS: 234 UK acute hospitals each prospectively identified 40 consecutive acute COPD admissions, documenting process of care and outcomes from a retrospective case note audit. Units also completed a resources and organisation of care proforma. RESULTS: Data for 7529 patients were received. Inpatient mortality was 7.4% and mortality at 90 days was 15.3%; the readmission rate was 31.4%. Mean length of stay for discharged patients was 8.7 days (median 6 days). Wide variation was observed in all outcomes between hospitals. Both inpatient mortality (odds ratio (OR) 0.67, CI 0.50 to 0.90) and 90 day mortality (OR 0.75, CI 0.60 to 0.94) were associated with a staff ratio of four or more respiratory consultants per 1000 hospital beds. The length of stay was reduced in units with more respiratory consultants, better organisation of care scores, an early discharge scheme, and local COPD management guidelines. CONCLUSIONS: Units with more respiratory consultants and better quality organised care have lower mortality and reduced length of hospital stay. This may reflect unit resource richness. Dissemination of good organisational practice and recruitment of more respiratory specialists offers the potential for improved outcomes for hospitalised COPD patients.

Acute Disease↗

Differential expression of PDE4 cAMP phosphodiesterase isoforms in inflammatory cells of smokers with COPD, smokers without COPD, and nonsmokers.

The expression profile of a panel of 15 cAMP phosphodiesterase isoforms was determined for inflammatory cell types of relevance to chronic obstructive pulmonary disease (COPD). In particular, the expression profiles for bronchoalveolar macrophages, peripheral blood monocytes, T lymphocytes, and neutrophils from smokers with and without COPD were compared. The phosphodiesterase expression profile was also analyzed for peripheral blood monocytes, T lymphocytes, and neutrophils from nonsmokers and compared with smokers. Qualitative RT-PCR identified transcripts for PDE4A10, PDE4A7, PDE4B1, PDE4B2, PDE4D1, and PDE4D2 isoforms as well as transcripts for both PDE3B and PDE7A in T cells, monocytes, and macrophages in all subjects. Transcripts for PDE4B3 and PDE4D4 were not observed in any of the cell types investigated. PDE4C was detected in all cells analyzed except for T cells. The long PDE4A4, PDE4D3, and PDE4D5 isoforms exhibited cell type-specific expression patterns. Semiquantitative and real-time quantitative RT-PCR were used to analyze differential expression between disease states and between cell types. PDE4A4 was found significantly upregulated in lung macrophages from smokers with COPD when compared with control smokers. Furthermore, PDE4A4 as well as PDE4B2 transcripts were detected in higher amounts in peripheral blood monocytes of smokers when compared with nonsmokers. Finally, PDE4D5 and PDE4C were differentially regulated in lung macrophages when compared with monocytes of the same subjects, irrespective of the disease state. The data obtained suggest that PDE4A4 may be relevant as a macrophage-specific anti-inflammatory target for COPD.

3',5'-Cyclic-AMP Phosphodiesterases↗

Determination of the etiological organism during acute exacerbations of COPD and efficacy of azithromycin, ampicillin-sulbactam, ciprofloxacin and cefaclor. Turkish Thoracic Society COPD Working Group.

Acute exacerbations, most of which are due to lower respiratory tract infections, cause great morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD) and most of these are due to lower respiratory tract infections. The aim of this study was to determine the causative organism and the effects of azithromycin, ampicillin sulbactam (sultamicillin), ciprofloxacin and cefaclor monohydrate therapy in COPD. One hundred and six patients with COPD in acute exacerbation were randomized into four groups for empiric antibiotic treatment following lung function tests and sputum examination. The most common strains isolated from sputum were Haemophilus influenzae (30.8%), Streptoccocus pneumoniae (12%) and Moraxella catarrhalis (7.7%). Azithromycin, sultamicillin, ciprofloxacin and cefaclor monohydrate were found to be effective in treating COPD exacerbations.

Ampicillin↗

Health status measurement in COPD: the minimal clinically important difference of the clinical COPD questionnaire.

BACKGROUND: Patient-reported outcomes (PRO) questionnaires are being increasingly used in COPD clinical studies. The challenge facing investigators is to determine what change is significant, ie what is the minimal clinically important difference (MCID). This study aimed to identify the MCID for the clinical COPD questionnaire (CCQ) in terms of patient referencing, criterion referencing, and by the standard error of measurement (SEM). METHODS: Patients were > or = 40 years of age, diagnosed with COPD, had a smoking history of >10 pack-years, and were participating in a randomized, controlled clinical trial comparing intravenous and oral prednisolone in patients admitted with an acute exacerbation of COPD. The CCQ was completed on Days 1-7 and 42. A Global Rating of Change (GRC) assessment was taken to establish the MCID by patient referencing. For criterion referencing, health events during a period of 1 year after Day 42 were included in this analysis. RESULTS: 210 patients were recruited, 168 completed the CCQ questionnaire on Day 42. The MCID of the CCQ total score, as indicated by patient referencing in terms of the GRC, was 0.44. The MCID of the CCQ in terms of criterion referencing for the major outcomes was 0.39, and calculation of the SEM resulted in a value of 0.21. CONCLUSION: This investigation, which is the first to determine the MCID of a PRO questionnaire via more than one approach, indicates that the MCID of the CCQ total score is 0.4.

Administration, Oral↗

Efficacy of inhaled steroids in undiagnosed subjects at high risk for COPD: results of the detection, intervention, and monitoring of COPD and asthma program.

BACKGROUND AND AIM: COPD leads to a progressive decline of pulmonary function. Family physicians treat a substantial number of patients with COPD and are encouraged to start treatment at as early a stage as is possible. This study analyzed the effectiveness of early inhaled corticosteroid treatment on the decline of pulmonary function in COPD patients. PATIENTS AND SETTING: Subjects with a rapid decline in lung function (ie, FEV(1) decline, > 80 mL/yr) who had never before received a diagnosis of asthma or COPD. METHODS: Two-year, randomized, controlled, double-blind clinical trial of fluticasone propionate (250 microg bid; 24 patients) or placebo (25 patients), followed by a 7-month open-label study in which all subjects received fluticasone propionate. The primary outcome was the post-bronchodilator therapy FEV(1,) and secondary outcomes were respiratory symptoms, exacerbations, health state, quality of life, and health-care utilization. RESULTS: After 31 months, there were no statistical differences in post-bronchodilator therapy FEV(1) between the intervention group and the control group. No statistical differences were observed for symptoms, exacerbations, or quality of life, although tendencies were consistently in favor of treatment. There was no significant impact on the direct or indirect costs. CONCLUSIONS: There are no indications that early treatment with inhaled corticosteroids modifies a rapid decline in lung function or respiratory symptoms and quality of life.

Administration, Inhalation↗

Does quality of life of COPD patients as measured by the generic EuroQol five-dimension questionnaire differentiate between COPD severity stages?

OBJECTIVE: To assess the discriminative properties of the EuroQol five-dimension questionnaire (EQ-5D) with respect to COPD severity according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria in a large multinational study. METHODS: Baseline EQ-5D visual analog scale (VAS) scores, EQ-5D utility scores, and St. George Respiratory Questionnaire scores were obtained from a subset of patients in the Understanding the Potential Long-term Impact on Function with Tiotropium trial, which was a 4-year placebo-controlled trial designed to assess the effect of tiotropium on the rate of decline in FEV(1) in COPD patients aged > or = 40 years, an FEV(1) of < 70% predicted, an FEV(1)/FVC ratio of < or = 70%, and a smoking history of >/= 10 pack-years. RESULTS: A total of 1,235 patients (mean post bronchodilator FEV(1), 48.8% predicted) from 13 countries completed the EQ-5D. The EQ-5D VAS and utility scores differed significantly among patients in GOLD stages 2, 3, and 4, also after correction for age, sex, smoking, body mass index (BMI), and comorbidity (p < 0.001). The mean EQ-5D VAS scores for patients in GOLD stages 2, 3, and 4 were 68 (SD, 16), 62 (SD, 17), and 58 (SD, 16), respectively. The mean utility scores were 0.79 (SD, 0.20) for patients in GOLD stage 2, 0.75 (SD, 0.21) for patients in GOLD stage 3, and 0.65 (SD, 0.23) for patients in GOLD stage 4. Effect sizes for the difference in utility scores between patients in GOLD stages 3 and 4 were more than twice as high as those for the difference between patients in GOLD stages 2 and 3. Gender, postbronchodilator FEV(1) percent predicted, the number of hospital admissions and emergency department visits in the year prior to baseline measurements, measures of comorbidity, and BMI were independently associated with EQ-5D utility. EQ-5D utility scores also differed between patients from different countries. French patients especially had lower utility scores than US patients. Utility scores calculated with the US value set were on average 5% higher than those calculated with the UK value set. CONCLUSIONS: Increasing severity of COPD was associated with a significant decline in EQ-5D VAS scores and utility scores. These results demonstrate that a generic instrument can assess COPD impact on quality of life and that the scores discriminate between patient groups of known severity. These utility scores will be useful in cost-effectiveness assessments.

Activities of Daily Living↗

Relationship between bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD. Study Group of Bacterial Infection in COPD.

STUDY OBJECTIVES: To investigate the possible relationship between functional respiratory impairment measured by FEV1 and isolation of diverse pathogens in the sputum of patients with exacerbations of COPD. DESIGN: Multicenter, cross-sectional, epidemiologic study. SETTING: Pneumology units in six secondary or tertiary hospitals in Spain. PATIENTS: Ninety-one patients with acute exacerbation of COPD were included. INTERVENTIONS: A quantitative sputum culture was performed, and bacterial growth was considered significant only when the germ was isolated at concentrations > 10(6) cfu (> 10(5) for Streptococcus pneumoniae) in samples with < 10 epithelial cells and > 25 leukocytes per low magnification field (x 100). RESULTS: Germs isolated were the following: Haemophilus influenzae (20 cases; 22%), Pseudomonas aeruginosa (14 cases; 15%), S. pneumoniae (9 cases; 10%), Moraxella catarrhalis (8 cases; 9%), other gram-negative bacteria (7 cases; 7%), and non-potentially pathogenic microorganisms (non-PPMs; 33 cases; 36%). P. aeruginosa and H. influenzae were isolated more frequently among the patients with FEV1 < 50% than among those with FEV1 > 50% (p < 0.05). All patients with P. aeruginosa in sputum had FEV1 < 1,700 mL. FEV1 < 50% was associated with a very high risk of P. aeruginosa or H. influenzae isolation: the odds ratios (ORs) are 6.62 (95% confidence interval [CI], 1.2 to 123.6) and 6.85 (95% CI, 1.6 to 52.6), respectively. Furthermore, active tobacco smoking was associated with a high risk of H. influenzae isolation (OR, 8.1; 95% CI, 1.9 to 43.0). CONCLUSIONS: Patients with the greatest degree of functional impairment, as measured by their FEV1, presented a higher probability of having an isolation of P. aeruginosa or H. influenzae in significant concentrations in sputum during an exacerbation. The diagnostic yield of sputum in patients with an FEV1 > 50% was low, with a predominance of non-PPMs. Low FEV1 and active tobacco smoking are data that should be considered when establishing an empiric antibiotic treatment for exacerbated COPD.

Aged↗

A randomized controlled trial on office spirometry in asthma and COPD in standard general practice: data from spirometry in Asthma and COPD: a comparative evaluation Italian study.

STUDY OBJECTIVES: To evaluate whether office spirometry by general practitioners (GPs) is feasible and may improve the diagnosis of asthma and COPD. METHODS: A prospective, randomized, comparative trial was planned involving 57 Italian pulmonology centers and 570 GPs who had to enroll consecutive subjects aged 18 to 65 years with symptoms of asthma or COPD without a previous diagnosis. Patients were randomized 1:1 into two groups with an interactive voice responding system: conventional evaluation alone vs conventional evaluation and spirometry. Office spirometry was performed by GPs who were trained by reference specialists using a portable electronic spirometer (Spirobank Office; MIR; Rome, Italy). Diagnosis was confirmed by the reference specialist center in blind fashion. RESULTS: Seventy-four GPs complied to the trial. Of 333 patients enrolled, 136 nonrandom violators completed the protocol. Per-protocol analysis showed a concordant diagnosis between GPs and specialists in 78.6% of cases in the conventional evaluation-plus-spirometry group vs 69.2% in the conventional evaluation group (p = 0.35). In the intention-to-treat analysis, the respective percentages of concordant diagnosis were 57.9 and 56.7 (p = 0.87). CONCLUSIONS: Office spirometry by GPs is feasible, but frequent protocol violation and inadequate sample size did not allow us to prove a significant advantage of office spirometry in improving the diagnosis of asthma and COPD in standard general practice as organized at present in Italy, thus reinforcing the need for close cooperation between GPs and specialists in respiratory medicine.

Adult↗