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Rationale: Recent cohort studies in chronic obstructive pulmonary disease (COPD) have questioned the validity of previously reported associations between inhaled corticosteroids (ICS) and reductions in mortality and rehospitalization in observational studies. Using time-dependent versions of statistical survival models, these studies have suggested immortal time bias as responsible for the proposed beneficial association. Objectives: We explored the extent of this bias in a study of patients with COPD monitored for a year from COPD discharge with two designs free of any immortal time bias in the General Practice Research Database in the United Kingdom. Methods: In Design 1, we used only patients whose treatment status was defined on the same day of discharge to obtain a matched cohort based on propensity scores, which were derived from the patient-level baseline characteristics. In Design 2, we identified all in the study cohort who experienced death or rehospitalization and then matched each case to up to four noncases by randomly sampling from the cohort risk sets without regard to treatment status. Measurements and Main Results: The propensity scores matched cohort analysis of 786 patients without a wait time found a significant risk reduction associated with use of ICS: hazard ratio, 0.69 (95% confidence interval, 0.52-0.93). The matched nested case-control analysis of 2,222 patients, designed without regard to exposure status and hence free of immortal time bias, gave a similar association with exposure to ICS in the last 6-month period: hazard ratio, 0.71 (0.56-0.90). Conclusions: We conclude that immortal time bias cannot account for the risk reduction associated with ICS exposure in observational studies. [ABSTRACT FROM AUTHOR]

Study Objectives: The nonproportional Venn diagram of obstructive lung disease (OLD) produced for the 1995 American Thoracic Society guidelines has not been quantified. We aim to quantify the proportion of the general population with OLD and the intersections of physician-diagnosed asthma, chronic bronchitis, and emphysema in the United States and the United Kingdom, and to examine the relationship to obstructive spirometry.Design and Participants: We analyzed data from the US National Health and Nutrition Examination (NHANES) III survey (1988 to 1994) and the UK General Practice Research Database for the year 1998.Results: The areas of intersection among the three OLD conditions produced seven mutually exclusive disease groups. The asthma-only group was the largest proportion of OLD patients, accounting for 50.3% and 79.4% of all OLD patients in the United States and the United Kingdom, respectively, and decreased with increasing age. Overall, 17% and 19% of OLD patients in the United States and in the United Kingdom, respectively, reported more than one OLD condition, and this percentage increased with age. According to the spirometry data from NHANES III, only 37.4% of emphysema-only patients had objective airflow obstruction. The prevalence of airflow obstruction was significantly higher among participants with combinations of emphysema and chronic bronchitis (57.7%), with emphysema and asthma (51.9%), and with all three OLD diseases concomitantly (52.0%).Conclusion: Concomitant diagnosis of asthma, chronic bronchitis, or emphysema is common among OLD patients from the general population, particularly in adults aged > or = 50 years. [ABSTRACT FROM AUTHOR]

We have compared bronchodilator dose-response curves to inhaled salbutamol in seven normal and eight asthmatic subjects. In all normal subjects maximal bronchodilatation measured by partial flow volume curves was achieved at a cumulative dose of 110 micrograms. The dose necessary to produce half maximal response (ED50) was 23 +/- 2 micrograms (mean +/- s.e. mean) with a range of 18-28 micrograms. In asthmatic subjects maximal bronchodilatation measured by FEV1 and by maximal flow volume curves was achieved at significantly higher (P less than 0.01) doses of salbutamol with a mean ED50 of 83 +/- 28 micrograms and range of 25-251 micrograms. There was a significant (P less than 0.05) correlation between ED50 and % predicted baseline FEV1. This is more likely to reflect impaired access of drug for airway beta- adrenoceptors than impaired beta-adrenoceptor function in asthma. In five asthmatic subjects dose-response curves to salbutamol and isoprenaline were compared and found to be similar, thus providing no evidence that salbutamol is a partial agonist in vivo, as it appears to be in vitro. [ABSTRACT FROM AUTHOR]

COPD has become a more popular research area in the last 3 decades, yet the first clear descriptions of acute and chronic bronchitis were in 1808. This brief history, comprehensively referenced, leads us through the early developments in respiratory physiology and their applications. It emphasises the early history of chronic bronchitis and emphysema in the 19(th) and early 20(th) centuries, long before the dominant effects of cigarette smoking emerged. This remains relevant to developing countries today.

Background: The forced oscillation technique (FOT) measures respiratory resistance and reactance; however, the upper airways may affect the results. We quantified the impact of glottal aperture and buccal air leaks., Methods: In the glottal aperture study (1) 10 healthy subjects (aged 34 ± 2 years) performed a total lung capacity maneuver followed by 10-s breath-hold with and without total glottal closure and (2) the effects of humming (incomplete glottal narrowing) on FOT measurements were studied in six healthy subjects. Glottal narrowing was confirmed by direct rhinolaryngoscopy. In the air leak study, holes of increasing diameter (3.5, 6.0, and 8.5 mm) were made to the breathing filters. Eleven healthy subjects (aged 33 ± 2 years) and five patients with COPD (aged 69 ± 3 years) performed baseline FOT measurements with the three modified filters., Results: Narrow glottal apertures and humming generated whole-breath resistance at 5 Hz (R5) peaks, increased R5 (1.49 ± 0.37 kPa/L/s vs 0.34 ± 0.01 kPa/L/s, P < .001), and decreased whole-breath reactance at 5 Hz (X5) values (-2.10 ± 0.51 kPa/L/s vs -0.09 ± 0.01 kPa/L/s, P < .001). The frequency dependency of resistance was increased. Holes in the breathing filters produced indentations on the breathing trace. Even the smaller holes reduced R5 in healthy subjects (0.33 ± 0.02 to 0.24 ± 0.02 kPa/L/s, P < .01) and patients with COPD (0.50 ± 0.04 to 0.41 ± 0.04 kPa/L/s, P < .05), whereas X5 became less negative (from -0.09 ± 0.01 to -0.05 ± 0.01 in healthy subjects, P < .01; from -0.22 ± 0.06 to -0.11 ± 0.03 kPa/L/s in patients with COPD, P < .05)., Conclusions: Visual inspection of the data is required to exclude glottal narrowing and buccal air leaks identified as R5 peaks and volume indentations, respectively, because these significantly affect FOT measurements.

The single-breath carbon monoxide diffusing capacity (DL(CO)) is the product of two measurements during breath holding at full inflation: (1) the rate constant for carbon monoxide uptake from alveolar gas (kco [minute(-1)]) and (2) the "accessible" alveolar volume (Va). kco expressed per mm Hg alveolar dry gas pressure (Pb*) as kco/Pb*, and then multiplied by Va, equals Dl(CO); thus, Dl(CO) divided by Va (DL(CO)/Va, also called Kco) is only kco/Pb* in different units, remaining, essentially, a rate constant. The notion that DL(CO)/Va "corrects" DL(CO) for reduced Va is physiologically incorrect, because DL(CO)/Va is not constant as Va changes; thus, the term Kco reflects the physiology more appropriately. Crucially, the same DL(CO) may occur with various combinations of Kco and Va, each suggesting different pathologies. Decreased Kco occurs in alveolar-capillary damage, microvascular pathology, or anemia. Increased Kco occurs with (1) failure to expand normal lungs to predicted full inflation (extrapulmonary restriction); or (2) increased capillary volume and flow, either globally (left-to-right intracardiac shunting) or from flow and volume diversion from lost or damaged units to surviving normal units (e.g., pneumonectomy). Decreased Va occurs in (1) reduced alveolar expansion, (2) alveolar damage or loss, or (3) maldistribution of inspired gases with airflow obstruction. Kco will be greater than 120% predicted in case 1, 100-120% in case 2, and 40-120% in case 3, depending on pathology. Kco and Va values should be available to clinicians, as fundamental to understanding the clinical implications of DL(CO). The diffusing capacity for nitric oxide (DL(NO)), and the DL(NO)/DL(CO) ratio, provide additional insights.

Reduction in total lung capacity (TLC) in obese men is associated with restricted expansion of the thoracic cavity at full inflation. We hypothesized that thoracic expansion was reduced by the load imposed by increased total trunk fat volume or its distribution. Using MRI, we measured internal and subcutaneous trunk fat and total abdominal and thoracic volumes at full inflation in 14 obese men [mean age: 52.4 yr, body mass index (BMI): 38.8 (range: 36-44) kg/m(2)] and 7 control men [mean age: 50.1 yr, BMI: 25.0 (range: 22-27.5) kg/m(2)]. TLC was measured by multibreath helium dilution and was restricted (<80% of the predicted value) in six obese men (the OR subgroup). All measurements were made with subjects in the supine position. Mean total trunk fat volume was 16.65 (range: 12.6-21.8) liters in obese men and 6.98 (range: 3.0-10.8) liters in control men. Anthropometry and mean total trunk fat volumes were similar in OR men and obese men without restriction (the ON subgroup). Mean total intraabdominal volume was 9.41 liters in OR men and 11.15 liters in ON men. In obese men, reduced thoracic expansion at full inflation and restriction of TLC were not inversely related to a large volume of 1) intra-abdominal or total abdominal fat, 2) subcutaneous fat volume around the thorax, or 3) total trunk fat volume. In addition, trunk fat volumes in obese men were not inversely related to gas volume or estimated intrathoracic volume at supine functional residual capacity. In conclusion, this study failed to support the hypotheses that restriction of TLC or impaired expansion of the thorax at full inflation in middle-aged obese men was simply a consequence of a large abdominal volume or total trunk fat volume or its distribution.

Restriction of total lung capacity (TLC) is found in some obese subjects, but the mechanism is unclear. Two hypotheses are as follows: 1) increased abdominal volume prevents full descent of the diaphragm; and 2) increased intrathoracic fat reduces space for full lung expansion. We have measured total intrathoracic volume at full inflation using magnetic resonance imaging (MRI) in 14 asymptomatic obese men [mean age 52 yr, body mass index (BMI) 35-45 kg/m2] and 7 control men (mean age 50 yr, BMI 22-27 kg/m2). MRI volumes were compared with gas volumes at TLC. All measurements were made with subjects supine. Obese men had smaller functional residual capacity (FRC) and FRC-to-TLC ratio than control men. There was a 12% predicted difference in mean TLC between obese (84% predicted) and control men (96% predicted). In contrast, differences in total intrathoracic volume (MRI) at full inflation were only 4% predicted TLC (obese 116% predicted TLC, control 120% predicted TLC), because mediastinal volume was larger in obese than in control [heart and major vessels (obese 1.10 liter, control 0.87 liter, P=0.016) and intrathoracic fat (obese 0.68 liter, control 0.23 liter, P<0.0001)]. As a consequence of increased mediastinal volume, intrathoracic volume at FRC in obese men was considerably larger than indicated by the gas volume at FRC. The difference in gas volume at TLC between the six obese men with restriction, TLC<80% predicted (OR), and the eight obese men with TLC>80% predicted (ON) was 26% predicted TLC. Mediastinal volume was similar in OR (1.84 liter) and ON (1.73 liter), but total intrathoracic volume was 19% predicted TLC smaller in OR than in ON. We conclude that the major factor restricting TLC in some obese men was reduced thoracic expansion at full inflation.

Background: The usual analysis of forced oscillometry measures respiratory resistance (Rrs) and reactance (Xrs) averaged over several tidal breaths (whole-breath analysis). Recent within-breath analyses have separated Rrs and Xrs into their mean inspiratory and mean expiratory components (inspiratory-expiratory breath analysis) but these have not been used to compare patients with asthma and those with chronic obstructive pulmonary disease (COPD). Large inspiratory-expiratory variations in Xrs at 5 Hz (DeltaX5) in an individual have been used as a surrogate marker of expiratory flow limitation., Methods: Whole-breath and inspiratory-expiratory impulse oscillometry was assessed in 34 patients with asthma (49 + or - 3 years; 15 male, forced expiratory volume in 1 s (FEV(1)) 69 + or - 4% predicted), 48 patients with COPD (64 + or - 2 years; 32 male, FEV(1) 59 + or - 3% predicted) and 18 normal subjects (37 + or - 2 years; 8 male)., Results: Whole-breath analysis failed to discriminate between patients with asthma and patients with COPD either for all patients or for patients with FEV(1) <60% predicted. Inspiratory-expiratory analysis in patients with FEV(1) <60% predicted showed that in the COPD group mean expiratory X5 (-0.44 + or - 0.04 kPa/l/s) was greater than inspiratory X5 (-0.23 + or - 0.02 kPa/l/s, p<0.001) whereas patients with asthma did not show such changes (-0.36 + or - 0.07 kPa/l/s vs -0.26 + or - 0.03 kPa/l/s, p=0.23). Even though DeltaX5 was larger in patients with COPD (0.21 + or - 0.03 kPa/l/s) than in patients with asthma (0.10 + or - 0.07 kPa/l/s), this was not significant (p=0.15)., Conclusions: Whole-breath impulse oscillation system analysis failed to discriminate between patients with asthma and those with COPD. Inspiratory-expiratory X5 analysis differentiated patients with asthma from those with COPD presumably reflecting enhanced dynamic airway narrowing on expiration in COPD. Further studies are needed to confirm these differences and investigate their cause.

Epidemiological studies have indicated that chronic obstructive pulmonary disease (COPD) may be associated with an increased incidence of ischaemic cardiac events. The current authors performed a post hoc analysis of the European Respiratory Society's study on Chronic Obstructive Pulmonary Disease (EUROSCOP); a 3-yr, placebo-controlled study of an inhaled corticosteroid budesonide 800 microg.day(-1) in smokers (mean age 52 yrs) with mild COPD. The current study evaluates whether long-term budesonide treatment attenuates the incidence of ischaemic cardiac events, including angina pectoris, myocardial infarction, coronary artery disorder and myocardial ischaemia. Among the 1,175 patients evaluated for safety, 49 (4.2%) patients experienced 60 ischaemic cardiac events. Patients treated with budesonide had a significantly lower incidence of ischaemic cardiac events (18 out of 593; 3.0%) than those receiving placebo (31 out of 582; 5.3%). The results of the present study support the hypothesis that treatment with inhaled budesonide reduces ischaemic cardiac events in patients with mild chronic obstructive pulmonary disease.

Although chronic obstructive pulmonary disease (COPD) patients frequently report symptoms, it is not known which factors determine the course of symptoms over time and if these differ according to the sex of the patient. The current study investigated predictors for presence, development and remission of COPD symptoms in 816 males and 312 females completing 3-yr-follow-up in the European Respiratory Society Study on Chronic Obstructive Pulmonary Disease (EUROSCOP). The following were included in generalised estimating equations logistic regression analyses: explanatory variables of treatment; pack-yrs smoking; age, forced expiratory volume in one second % predicted (FEV1 % pred); annual increase in FEV1 and number of cigarettes smoked; body mass index; and phadiatop. Interaction terms of sex multiplied by explanatory variables were tested. Over 3 yrs, similar proportions of males and females reported symptoms. In males only, higher FEV1 % pred was associated with reduction in new symptoms of wheeze and dyspnoea, and symptom prevalence was reduced with annual FEV1 improvement and phlegm prevalence reduced with budesonide treatment (odds ratio 0.66; 95% confidence interval 0.52-0.83). Additionally an increase in the number of cigarettes smoked between visits increased the risk of developing phlegm (1.40 (1.14-1.70)) and wheeze (1.24 (1.03-1.51)) in males but not females. The current study shows longitudinally that symptom reporting is similar by sex. The clinical course of chronic obstructive pulmonary disease can differ by sex, as males show greater response to cigarette exposure and treatment.

Background: There is increasing appreciation of gender differences in COPD but scant data whether risk factors for low lung function differ in men and women. We analysed data from 3 years follow-up in 178 women and 464 men with COPD, participants in the Euroscop Study who were smokers unexposed to inhaled corticosteroids., Methods: Explanatory variables of gender, age, starting age and pack-years smoking, respiratory symptoms, FEV(1)%FVC and FEV(1)%IVC (clinically important measures of airway obstruction), body mass index (BMI), and change in smoking were included in multiple linear regression models with baseline and change in post-bronchodilator FEV(1) as dependent variables., Results: Reduced baseline FEV(1) was associated with respiratory symptoms in men only. Annual decline in FEV(1) was not associated with respiratory symptoms in either men or women, and was 55 ml less in obese men (BMI 30 kg/m(2)) than men having normal BMI, an effect not seen in women. It was 32 ml faster in women with FEV(1)%FVC

Progression of chronic obstructive pulmonary disease (COPD) has been studied predominantly by following change in forced expiratory volume in 1s (FEV1) which reflects both primary airway disease and associated alveolar disease. Carbon monoxide transfer (Tlco) (the product of the transfer coefficient Kco and alveolar volume Va) is the only simple, widely available test of alveolar function, but few studies have followed long-term changes in an individual. Seventeen middle-aged men with moderate chronic airflow obstruction (mean FEV1 56% of predicted values) were observed with yearly measurements of FEV1, Tlco and Kco over a mean of 18.9 yr. At the end of follow-up FEV1 had fallen to 29% of predicted values. Va, measured by single breath dilution, fell in each man. Kco at recruitment ranged from 41% to 110% predicted and remained >75% predicted in eight men at the end of follow-up supporting a phenotype of COPD with predominant airway disease and little emphysema. Fall in FEV1 was faster (2.03% predicted FEV1/yr) in seven men with low initial Kco<75% pred. than in men with initial Kco>75% pred. (1.14% predicted FEV1/yr, P=0.006). Repeated measurements of CO transfer in an individual should increase the present poor knowledge of the contribution of alveolar disease to the progression of chronic airflow obstruction.

Single constant flow exhaled nitric oxide (eNO) cannot distinguish between the sources of NO. The present study measured eNO at multiple expired flows (MEFeNO) to partition NO into alveolar (Calv,NO) and bronchial (Jaw,NO) fractions to investigate peripheral lung contribution to eNO in chronic obstructive lung disease (COPD). MEFeNO were made in 81 subjects including 18 nonsmokers, 16 smokers and 47 COPD patients of different severity by the classification of the Global Initiative for Chronic Obstructive Lung Disease (GOLD): 0 (n = 14), 1 (n = 7), 2 (n = 11), 3 (n = 8) and 4 (n = 7). COPD severity was correlated with an increased Calv,NO regardless of the patient's smoking habit or current treatment. The levels of Calv,NO (in ppb) were 1.4+/-0.09 in nonsmokers, 2.1+/-0.1 in smokers categorised as GOLD stage 0 (smokers-GOLD0), 3.3+/-0.18 in GOLD1-2 and 3.4+/-0.1 in GOLD3-4. Jaw,NO levels (pL x s(-1)) were higher in nonsmokers than smokers-GOLD0 (716.2+/-33.3 versus 464.7+/-41.8), GOLD3-4 (609.4+/-71). Diffusion of NO in the airways (Daw,NO pL x ppb(-1) s(-1)) was higher (p<0.05) in GOLD3-4 than in nonsmokers (15+/-1.2 versus 11+/-0.5) and smokers-GOLD0 (11.6+/-0.5). MEFeNO measurements were reproducible, free from day-to-day and diurnal variation and were not affected by bronchodilators. In conclusion, chronic obstructive pulmonary disease is associated with elevated alveolar nitric oxide. Measurements of nitric oxide at multiple expired flows may be useful in monitoring inflammation and progression of chronic obstructive pulmonary disease, and the response to anti-inflammatory treatment.

The interrupter technique, the simplest method for measuring airflow resistance (R(int)) is particularly valuable under field conditions. We investigate whether during tidal breathing, variations in the flow at which interruption occurs contribute to variability of results. Using a portable device with mouthpiece, sets of 10 measurements of R(int) (R(int,mo)) were made in inspiration and expiration at 0.05 l s(-1) intervals from 0.1 up to 0.9 l s(-1) flow in 22 normal adults, 11 children (5-9 years) and 12 COPD patients. R(int) was also measured via nasal-mask in normal adults (R(int,na)). Intra-subject coefficient of variation was obtained at each flow and flow-dependence of R(int) was assessed. In normal subjects, R(int)-flow relationships were consistent, with a narrow range of absolute values. R(int,na), but not R(int,mo), rose with increasing flow, especially >0.4 l s(-1). Repeatability was poor at flows <0.3 l s(-1) but improved with increasing flow and was better in inspiration than expiration. In children, repeatability was better than in adults and R(int,mo) was not flow dependent at < or =0.4 l s(-1). By contrast, in COPD patients repeatability was less good and R(int,mo) increased with increasing flows. R(int,mo) and R(int,na) should be measured at fixed inspiratory flows. The best signal-to-noise ratios were obtained at 0.4 l s(-1) for R(int) in normal adults and COPD patients and at 0.3 l s(-1) in children.

Reduced functional residual capacity (FRC) is consistently found in obese subjects. In 10 obese subjects (mean +/- SE age 49.0 +/- 6 yr, weight 128.4 +/- 8 kg, body mass index 44 +/- 3 kg/m2) without respiratory disease, we examined 1) supine changes in total lung capacity (TLC) and subdivisions, 2) whether values of total respiratory resistance (Rrs) are appropriate for mid-tidal lung volume (MTLV), and 3) estimated resistance of the nasopharyngeal airway (Rnp) in both sitting and supine postures. The results were compared with those of 13 control subjects with body mass indexes of <27 kg/m2. Rrs at 6 Hz was measured by applying forced oscillation at the mouth (Rrs,mo) or the nose (Rrs,na); Rnp was estimated from the difference between sequential measurements of Rrs,mo and Rrs,na. All measurements were made when subjects were seated and when supine. Obese subjects when seated had a restrictive defect with low TLC and FRC-to-TLC ratio; when supine, TLC fell 80 ml and FRC fell only 70 ml compared with a mean supine fall of FRC of 730 ml in control subjects. Values of Rrs,mo and Rrs,na at resting MTLV in obese subjects were about twice those in control subjects in both postures. Relating total respiratory conductance (1/Rrs) to MTLV, the increase in Rrs,mo in obese subjects was only partly explained by their reduced MTLV. Rnp was increased in some obese subjects in both postures. Despite the increased extrapulmonary mass load in obese subjects, further falls in TLC and FRC when supine were negligible. Rrs,mo at isovolume was increased. Further studies are needed to examine the causes of reduced TLC and increases in Rrs,mo and sometimes in Rnp in obese subjects.

Introduction: Subjects with asthma frequently have nasal symptoms and complain of orthopnoea but airflow resistance is usually only assessed during oral breathing and while seated., Method: We have used a forced oscillation technique to measure total respiratory resistance (Rrs) at 6Hz during mouth breathing (Rrs,mo) and during nose breathing (Rrs,na) in the sitting and supine postures; resistance of the nasal airway (Rnaw) was estimated as Rrs,na--Rrs,mo. Forced oscillations were applied during normal tidal breathing and the mid-tidal lung volume (MTLV) was determined for each breathing route and posture., Subjects: Three groups of subjects were studied: 10 normal subjects without lung or nasal disease (N; five males, mean age 33.5 [range 23-58] years, mean FEV1 105%pred, FEV1/VC 86%); seven subjects with asthma alone (A; four males, 40.3 [23-57] years, mean FEV1 66%pred, FEV1/VC 74%); 10 asthmatic subjects with nasal obstructive symptoms (AN; six males, 62.8 [38-80] years, mean FEV1 56%pred, FEV1/VC 75%)., Results: In all three groups of subjects, mean Rrs,mo and Rrs,na were higher in the supine than sitting posture. In normal subjects the increase in supine Rrs,mo was associated with a 0.6 liter fall in MTLV. In asthma supine Rrs,mo increased despite a much smaller fall in MTLV; supine increases in Rrs,na were particularly large in presence of nasal disease., Discussion: Values of airflow resistance are 2-3 times higher in both normal and asthmatic subjects when breathing via the nose and supine than under normal laboratory conditions of oral breathing and seated.

Background: Although breathlessness is common in chronic heart failure (CHF), the role of inspiratory muscle dysfunction remains unclear. We hypothesised that inspiratory muscle endurance, expressed as a function of endurance time (Tlim) adjusted for inspiratory muscle load and inspiratory muscle capacity, would be reduced in CHF., Methods: Endurance was measured in 10 healthy controls and 10 patients with CHF using threshold loading at 40% maximal oesophageal pressure (Poes(max)). Oesophageal pressure-time product (PTPoes per cycle) and Poes(max) were used as indices of inspiratory muscle load and capacity, respectively., Results: Although Poes(max) was slightly less in the CHF group (-117.7 (23.6) v -100.0 (18.3) cm H(2)O; 95% CI -37.5 to 2.2 cm H(2)O, p = 0.1), Tlim was greatly reduced (1800 v 306 (190) s; 95% CI 1368 to 1620 s, p<0.0001) and the observed PTPoes per cycle/Poes(max) was increased (0.13 (0.05) v 0.21 (0.04); 95% CI -0.11 to -0.03, p = 0.001). Most of this increased inspiratory muscle load was due to a maladaptive breathing pattern, with a reduction in expiratory time (3.0 (5.8) v 1.1 (0.3) s; 95% CI 0.3 to 3.5 s, p = 0.03) accompanied by an increased inspiratory time relative to total respiratory cycle (Ti/Ttot) (0.43 (0.14) v 0.62 (0.07); 95% CI -0.3 to -0.1, p = 0.001). However, log Tlim, which incorporates the higher inspiratory muscle load to capacity ratio caused by this altered breathing pattern, was >/=85% predicted in seven of 10 patients., Conclusions: Although a marked reduction in endurance time was observed in CHF, much of this reduction was explained by the increased inspiratory muscle load to capacity ratio, suggesting that the major contributor to task failure was a maladaptive breathing pattern rather than impaired inspiratory muscle endurance.

Introduction: In patients with COPD who have recently been hospitalized for their disease, we examined whether treatment with inhaled corticosteroids without or with long-acting beta-adrenoceptor agonists (beta-agonists) reduced rehospitalization and mortality., Study Design: Retrospective cohort analysis in the UK General Practice Research Database., Methods: We compared rehospitalization for a COPD-related medical condition or death within 1 year after first hospitalization, in 3636 COPD patients receiving prescriptions for inhaled corticosteroids or long-acting beta-agonists compared with 627 reference patients with COPD who were prescribed short-acting bronchodilators only., Results: Rehospitalization within a year occurred in 13.2% of the reference COPD patients, 14.0% of users of long-acting beta-agonists only, 12.3% of users of inhaled corticosteroids only, and 10.4% of users of inhaled corticosteroids and long-acting beta-agonists. Death within a year occurred in 24.3% of the reference COPD patients, 17.3% of users of long-acting beta-agonists only, 17.1% of users of inhaled corticosteroids only, and in 10.5% of users of inhaled corticosteroids and long-acting beta-agonists. In multivariate analyses the risk of rehospitalization or death was reduced by 10% in users of long-acting beta-agonists only (NS), by 16% in users of inhaled corticosteroids only, and by 41% in users of combined inhaled corticosteroids and long-acting beta-agonists (both p < 0.05)., Conclusion: Use of inhaled corticosteroids with/without long-acting beta-agonists was associated with a reduction of rehospitalization or death in COPD patients.

Diaphragm function is compromised in severe chronic obstructive pulmonary disease (COPD) by hyperinflation, but its ability to shorten and contribute to tidal volume is uncertain. We estimated coronal diaphragm length by measuring zone of apposition length with ultrasound and rib cage diameters with magnetometers, in 10 male patients with severe COPD and 10 age- and sex-matched control subjects. Diaphragm length was 20% shorter in patients at residual volume (413 and 536 mm in patients and control subjects, respectively) and FRC (381 and 456 mm, respectively), but was not different at total lung capacity (312 and 336 mm, respectively). Zone of apposition length was reduced 50% at residual volume and FRC in patients, but was larger at a given absolute lung volume than in control subjects. There were no differences in tidal volume (0.8 L), tidal changes in zone of apposition length (20 mm) and diaphragm length (38 and 42 mm), and tidal volume displaced by the diaphragm (0.6 L), even though mean FRC in patients was similar to predicted total lung capacity. Although the diaphragm is shorter at FRC in patients with COPD, its motion and change in length during tidal breathing is similar to that in control subjects.

Despite substantial evidence regarding the benefits of combined use of inhaled corticosteroids and long-acting beta2-agonists in asthma, such evidence remains limited for chronic obstructive pulmonary disease (COPD). Observational data may provide an insight into the expected survival in clinical trials of fluticasone propionate (FP) and salmeterol in COPD. Newly physician-diagnosed COPD patients identified in primary care during 1990-1999 aged > or = 50 yrs, of both sexes and with regular prescriptions of respiratory drugs were identified in the UK General Practice Research Database. Three-year survival in 1,045 COPD patients treated with FP and salmeterol was compared with that in 3,620 COPD patients who regularly used other bronchodilators but not inhaled corticosteroids or long-acting beta2-agonists. Standard methods of survival analysis were used, including adjustment for possible confounders. Survival at year 3 was significantly greater in FP and/or salmeterol users (78.6%) than in the reference group (63.6%). After adjusting for confounders, the survival advantage observed was highest in combined users of FP and salmeterol (hazard ratio (HR) 0.48 (95% confidence interval 0.31-0.73)), followed by users of FP alone (HR 0.62 (0.45-0.85)) and regular users of salmeterol alone (HR 0.79 (0.58-1.07)) versus the reference group. Mortality decreased with increasing number of prescriptions of FP and/or salmeterol. In conclusion, regular use of fluticasone propionate alone or in combination with salmeterol is associated with increased survival of chronic obstructive pulmonary disease patients managed in primary care.

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.