Mindfulness-based stress reduction added to care as usual for lung cancer patients and/or their partners: A multicentre randomized controlled trial.

OBJECTIVE: Lung cancer patients report among the highest distress rates of all cancer patients. Partners report similar distress rates. The present study examined the effectiveness of additional mindfulness-based stress reduction (care as usual [CAU] + MBSR) versus solely CAU to reduce psychological distress in lung cancer patients and/or their partners. METHODS: We performed a multicentre, parallel-group, randomized controlled trial. Mindfulness-based stress reduction is an 8-week group-based intervention, including mindfulness practice and teachings on stress. Care as usual included anticancer treatment, medical consultations, and supportive care. The primary outcome was psychological distress. Secondary outcomes included quality of life, caregiver burden, relationship satisfaction, mindfulness skills, self-compassion, rumination, and posttraumatic stress symptoms. Outcomes were assessed at baseline, post-intervention, and 3-month follow-up. Linear mixed modeling was conducted on an intention-to-treat sample. Moderation (gender, disease stage, baseline distress, participation with/without partner) and mediation analyses were performed. RESULTS: A total of 31 patients and 21 partners were randomized to CAU + MBSR and 32 patients and 23 partners to CAU. After CAU + MBSR patients reported significantly less psychological distress (p = .008, d = .69) than after CAU. Baseline distress moderated outcome: those with more distress benefitted most from MBSR. Additionally, after CAU + MBSR patients showed more improvements in quality of life, mindfulness skills, self-compassion, and rumination than after CAU. In partners, no differences were found between groups. CONCLUSION: Our findings suggest that psychological distress in lung cancer patients can be effectively treated with MBSR. No effect was found in partners, possibly because they were more focused on patients' well-being rather than their own.

Maximal exercise capacity in chronic obstructive pulmonary disease: a limited indicator of the health status.

BACKGROUND: Dyspnoea and diminished functional status are pivotal features of the health status (HS) in chronic obstructive pulmonary disease (COPD). However, it is still not fully understood how pulmonary function tests and cardiopulmonary exercise testing relate to these aspects. This may be due to incomplete assessment and/or deficient definitions of HS. Especially regarding peak oxygen consumption, inconsistent results have been reported. OBJECTIVES: To determine the value of maximal cycle ergometry in relation to a broad spectrum of HS aspects. METHODS: 129 patients with COPD, stage II and III according to the GOLD classification, performed a cardiopulmonary exercise test. Sixteen independent sub-domains of HS were assessed according to the Nijmegen Integral Assessment Framework, covering physiological functioning, complaints, functional impairments and quality of life as main domains. VO(2)(max) and HS sub-domains were correlated by bivariate analysis. RESULTS: Weak correlations of VO(2)(max) with most sub-domains were found, except for exercise capacity; the other 5 sub-domains of physiological functioning did not correlate. Between different types of exercise limitation (5 types were differentiated), no significant differences were noted in the scores of 13/16 HS sub-domains. CONCLUSIONS: VO(2)(max) is indeed correlated with most aspects of HS, except for physiological variables, but associations are weak. No single exercise limitation type is associated with specific HS problems. Thus separate assessment of all HS sub-domains is advocated to ensure adequate planning of therapeutic interventions.

Predictive value of lung function below the normal range and respiratory symptoms for progression of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an insidiously starting disease. Early detection has high priority because of the possibility of early implementation of smoking cessation interventions. An evidence based model for case finding of COPD is not yet available. OBJECTIVE: To describe the early development of COPD, and to assess the predictive value of early signs (respiratory symptoms, lung function below the normal range, reversibility). DESIGN AND METHODS: In a prospective study, based in general practice, formerly undiagnosed subjects (n = 464) were assessed at baseline and at 5 years for respiratory symptoms and pulmonary function. Odds ratios for early signs were calculated (adjusted for age, gender, pack-years at baseline and smoking behaviour during follow-up), and defined as possible indicators of disease progression. RESULTS: Over a 5 year period, the percentage of subjects with obstruction increased from 7.5% (n = 35) at baseline to 24.8% (n = 115) at 5 years. The presence of mild early signs and lung function below the normal range at baseline were related to an increased risk of developing mild to moderate COPD (GOLD I: OR 1.87 (95% CI 1.22 to 2.87); GOLD II: OR 2.08 (95% CI 1.29 to 3.37) to 2.54 (95% CI 1.25 to 5.19)) at 5 years. CONCLUSION: Lung function below the normal range and early respiratory signs predict the development and progression of COPD.

Healthcare system design and parttime working doctors.

More doctors would like to work parttime. Since research on fitting healthcare system design with the structure of parttime jobs is lacking, we studied how parttime work for medical doctors could be enabled from a system design perspective. A theoretical analysis was performed, illustrated by two case studies. We conclude that introducing parttime work can provide the opportunity for improving system design and, therewith, performance. From the case studies it seems that work redesign can enable parttime work, and at the same time improve system performance. Better managing variability in the system contributed to this. The case studies results also showed that systems characterized by different levels of variability fit with different work contracts.

Ventolin Diskus and Inspyril Turbuhaler: an in vitro comparison.

Dose delivery (total emitted dose, or TED) from dry powder inhalers (DPIs), pulmonary deposition, and the biological effects depend on drug formulation and device and patient characteristics. The aim of this study was to measure, in vitro, the relationship between parameters of inhalation profiles recorded from patients, the TED and fine particle mass (FPM) of Diskus and Turbuhaler inhalers. Inhalation profiles (IPs) of 25 patients, a representative sample of a wide range of 1500 IPs generated by 10 stable asthmatics, 3 x 16 (mild/moderate/severe) COPD patients and 15 hospitalized patients with an exacerbation asthma or COPD, were selected for each device. These 25 IPs were input IPs for the Electronic Lung (a computerdriven inhalation simulator) to determine particle size distribution from Ventolin Diskus and Inspyril Turbuhaler. The TED and FPM of Diskus and FPM of Turbuhaler were affected by the peak inspiratory flow (PIF) and not by slope of the pressure-time curve, inhaled volume and inhalation time. This flow-dependency was more marked at lower flows (PIF < 40 L/min). Both the TED and FPM of Diskus were significantly higher as compared to those of the Turbuhaler [mean (SD) TED(_diskus) (%label claim) 83.5 (13.9) vs. TED(_turbuhaler) (72.5 (11.1) (p = 0.004), FPM(_diskus) (%label claim) 36.8 (9.8) vs FPM(_turbuhaler) (28.7 (7.7) (p < 0.05)]. The TED and FPM of Diskus and FPM of Turbuhaler were affected by PIF, the flow-dependency being greater at PIF values below 40 L/min. Lower PIFs occurred more often when using Turbuhaler than Diskus, since Turbuhaler have a higher resistivity, requires substantially higher pressure in order to generate the same flow as Diskus. TED, dose consistency and the FPM were higher for Diskus as compared to Turbuhaler. The flow dependency of TED and FPM was substantially influenced by inhalation profiles when not only profiles of the usual outpatient population were included but also the real outliers from exacerbated patients.

Self-management of asthma in general practice, asthma control and quality of life: a randomised controlled trial.

BACKGROUND: A study was undertaken to determine the effectiveness of asthma self-management in general practice. METHODS: Nineteen general practices were randomly allocated to usual care (UC) or self-management (SM). Asthma patients were included after confirmation of the GP diagnosis. Follow up was 2 years. Patients kept diary cards and visited the lung function laboratory every 6 months. Outcomes were number of successfully treated weeks, limited activity days, asthma specific quality of life, forced expiratory volume in 1 second (FEV(1)), FEV(1) reversibility, concentration of histamine provoking a fall in FEV(1) of 20% or more (PC(20) histamine), and amount of inhaled steroids. RESULTS: A total of 214 patients were included in the study (104 UC/110 SM; one third of the total asthma population in general practice); 62% were female. The mean percentage of successfully treated weeks per patient in the UC group was 72% (74/103 weeks) compared with 78% (81/105 weeks) in the SM group (p=0.003). The mean number of limited activity days was 1.2 (95% CI 0.5 to 1.9) in the SM group and 3.9 (95% CI 2.5 to 5.4) in the UC group. The estimated increase in asthma quality of life score was 0.10 points per visit in the UC group and 0.21 points per visit in the SM group (p=0.055). FEV(1), FEV(1) reversibility, and PC(20) histamine did not change. There was a saving of 217 puffs of inhaled steroid per patient in favour of the SM group (p<0.05). CONCLUSION: Self-management lowers the burden of illness as perceived by patients with asthma and is at least as effective as the treatment usually provided in Dutch primary care. Self-management is a safe basis for intermittent treatment with inhaled corticosteroids.

The cost effectiveness of early treatment with fluticasone propionate 250 microg twice a day in subjects with obstructive airway disease. Results of the DIMCA program.

In a two-stage detection program, subjects with signs of obstructive airway disease were selected from a random sample of the general population. Subjects (n = 82) were randomly assigned to either fluticasone propionate 250 microg twice a day or placebo twice a day via pMDI in a 1-yr, double-blind trial if they met criteria for persistent airway obstruction, increased bronchial hyperresponsiveness, or a rapid decline in FEV(1). Main outcome measures were postbronchodilator FEV(1), quality-adjusted life years (QALYs), and direct medical cost. Secondary measures were prebronchodilator FEV(1), PC(20), health-related quality of life (CRQ), symptom-free weeks, episode-free weeks, exacerbations, and indirect cost. Subgroup analysis was based on reversibility of obstruction. Analysis revealed a significant gain in postbronchodilator FEV(1) (98 ml/yr; p = 0.01) in favor of fluticasone. Only subjects with reversible obstruction showed an improvement in PC(20) (1.4 doubling dose; p = 0.03). Early treatment resulted in 2.7 QALYs gained per 100 treated subjects (p = 0.17) and in a clinically relevant improvement in dyspnea (CRQ; p < 0.03). The incremental cost effectiveness ratios were US$13,016/QALY for early treatment and US$33,921/QALY for the combination of detection and treatment. The incremental cost for one additional subject with a clinically relevant difference in dyspnea was US$1,674. In conclusion, early intervention with fluticasone resulted in significant health gains at relatively low financial cost.

Resistivities of placebo and active Diskus inhalers compared.

OBJECTIVE: Verbal instruction and demonstration of inhalation technique are essential to enhance the effectiveness of inhalation therapy. Placebo devices are commonly used to instruct patients. It is not obvious that patients, who inhale with an adequate flow through an empty placebo Diskus, would also be able to do so with active inhalers containing a strip with powder. The presence of powder may result in a change in resistivity. We compared the resistivities of a placebo Diskus being empty; a powder filled Diskus inhaler and a Diskus inhaler with an empty blister. METHODS: A Diskus inhaler was placed in a box, which enabled measurement of pressure drop and flow rates. Ten placebo and ten Ventolin Diskus inhalers were measured. Twelve pressure- and flow-profiles were recorded through each device. After each simulated inhalation through a powder filled blister, a second inhalation was performed through the empty blister. The resistivity was calculated by pressure-flow equation. RESULTS: The resistivity of the empty placebo Diskus inhaler was slightly but significantly higher than both blister filled inhalers, with or without powder (0.0215 vs. 0.0211 and 0.0211 (kPa)(0.5) (l min(-1))(-1)) (P<0.001). CONCLUSION: Patients who are capable of generating sufficient flow through a placebo Diskus will surely be capable of generating equivalent flows through a Diskus inhaler containing a strip with active drug substance.

Peak inspiratory flow rate and slope of the inhalation profiles in dry powder inhalers.

Aerosol delivery depends on device design and inhalation technique. In vitro device evaluations have shown that the emitted dose and fine particle mass of dry powder inhalers (DPIs) increase at high peak inspiratory flow rates (PIFR). Since the PIFR is mostly achieved after the release of the powder, slope of the pressure profile is also described as an important determinant. The aim of the present study was to assess whether the PIFR while using Diskus it and Turbuhaler it inhalers could be used to predict the slope of the inhalation pressure profile. In a group of 10 stable asthma patients and three groups (mild, moderate and severe) of 16 chronic obstructive pulmonary disease (COPD) patients, lung function was measured, and for each device, 18 inhalation profiles were recorded with the inhalation profile recorder during six sessions over 10 weeks. The values for the pressure slope and PIFR of both Diskus and Turbuhaler, were significantly correlated. The r-values were 0.865 and 0.882, respectively (p<0.01). Percentage explained variance was 74.8% for Diskus and 77.8% for Turbuhaler. Significant correlations were found between peak inspiratory flow rates and slopes. It has been shown for two different dry powder inhalers that peak inspiratory flow rate and slope correlate well in a wide range of patient groups.

Effect of inhaled corticosteroids on bronchial responsiveness in patients with "corticosteroid naive" mild asthma: a meta-analysis.

BACKGROUND: Inhaled corticosteroids are the most efficacious anti-inflammatory drugs in asthma. International guidelines also advocate the early introduction of inhaled corticosteroids in corticosteroid naive patients. A study was undertaken to assess the effects of inhaled corticosteroids on bronchial hyperresponsiveness in patients with corticosteroid naive asthma by conventional meta-analysis. METHODS: A Medline search of papers published between January 1966 and June 1998 was performed and 11 papers were selected in which the patients had no history of treatment with inhaled or oral corticosteroids. Bronchial responsiveness to bronchoconstricting agents was considered as the main outcome parameter. Doubling doses (DD) of histamine or methacholine were calculated. RESULTS: The total effect size of inhaled corticosteroids (average daily dose 1000 microg) versus placebo in the 11 studies was +1.16 DD (95% confidence interval (CI) +0.76 to +1.57). When only the eight short term studies (2-8 weeks) were analysed the effect size of the bronchoconstricting agent was +0.91 DD (95% CI +0.65 to +1.16). No relationship was found between the dose of inhaled corticosteroid used and the effect on bronchial responsiveness. CONCLUSION: This meta-analysis in patients with corticosteroid naive asthma indicates that, on average, high doses of inhaled corticosteroids decrease bronchial hyperresponsiveness in 2-8 weeks. It remains unclear whether there is a dose-response relationship between inhaled corticosteroids and effect on bronchial hyperresponsiveness.

The role of "fear of corticosteroids" in nonparticipation in early intervention with inhaled corticosteroids in asthma and COPD in general practice.

Treatment of chronic airflow obstruction with inhaled corticosteroids at an early stage has been shown to preserve the lung function. We tested the hypothesis that "fear of corticosteroids" may be an important reason for nonparticipation in the Detection, early Intervention and Monitoring programme on Chronic obstruction pulmonary disease (COPD) and Asthma ("DIMCA") project. One thousand seven hundred and forty nine adult subjects from 10 general practices were invited to participate in the several parts of the "DIMCA" programme. Refusers were questioned about the reason(s) for nonparticipation. Together the screening, monitoring and three drug interventions of the study showed on average 25-35% refusers. The most frequent reasons for nonparticipation were absence of pulmonary symptoms and lack of time. For those invited to take part in one of the three drug interventions, "dislike of medication" was the most important reason for nonparticipation (33, 45 and 67% of the refusers). "Fear of corticosteroids" specifically was the reason for nonparticipation in 8% of the refusers on the basis of "dislike of medication". We concluded that a specific fear of corticosteroids was not a major obstacle for early intervention with inhaled corticosteroids.

How to avoid underdiagnosed asthma/chronic obstructive pulmonary disease?

The prevalence of asthma and chronic obstructive pulmonary disease (COPD) is rising in most countries, including The Netherlands. It has been suggested that a majority of these cases of (self-reported) symptoms related to asthma/COPD are not diagnosed in general practice. We compared a population screening for underdiagnosed asthma/COPD with a high-risk approach by a questionnaire form with specified questions about asthma/COPD-related symptoms. A case-controlled study including a record review was performed of cases and controls. The results of a population screening were used to classify patients as (a) asthma/COPD, (b) at risk for asthma/COPD, or (c) no asthma/COPD. Eleven hundred fifty-five patients were screened. One hundred fifty-five patients reported previous asthma/COPD-related care (cases). The difference between number of cases and controls in asthma/COPD diagnosis was chosen as main outcome measure. The population screening revealed 85 subjects with a diagnosis of asthma/COPD and 154 subjects with an increased risk. Nineteen diagnoses could be made in cases, and eight diagnoses in controls. The chart review showed that only seven cases and two controls were known to the general practitioner. From this study it can be concluded that in order to reduce the number of un- and underdiagnosed patients, all listed patients in general practice should be screened. However, if screening of all patients is not feasible, active case finding by asking a few questions about shortness of breath or wheezing to all patients in the group of listed individuals is recommended.

Are anti-oxidant and anti-inflammatory treatments effective in different subgroups of COPD? A hypothesis.

The treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids or anti-oxidants is still under debate and the identification of sub-groups of COPD patients who may benefit from either anti-inflammatory or anti-oxidant treatment is needed. We re-analysed data from an earlier study of inhaled beclomethasone therapy in COPD (n = 28) and asthma (n = 28) patients in order to determine patient characteristics that predict a favourable inhaled steroid treatment effect. A higher bronchodilatory response, a faster decline of FEV1 prior to the treatment period and a lower Tiffeneau index were significantly related to more beneficial treatment effects. Increased smoking tended to be related to less steroid treatment benefits, though it was not statistically significant. In this paper these findings are presented in light of the available literature on anti-inflammatory and anti-oxidant COPD treatment. On this basis the hypothesis is presented that anti-oxidant treatment might be relatively more effective among those COPD patients who respond less well to inhaled steroids (low reversibility and heavy smoking).

Testing bronchial hyper-responsiveness: provocation or peak expiratory flow variability?

BACKGROUND: Assessing bronchial hyper-responsiveness (BHR) is a main diagnostic criterion of asthma. Provocation testing is not readily available in general practice, but peak expiratory flow (PEF) is. Several guidelines promote the use of PEF variability as a diagnostic tool for BHR. This study tested the agreement between histamine challenge testing and PEF variability, and the consequences for diagnosing asthma. AIM: To investigate the possibility of assessing BHR by PEF variability, using a histamine provocation test as a reference. METHOD: Subjects with signs of symptoms indicating asthma (persistent or recurrent respiratory symptoms or signs of reversible bronchial obstruction) (n = 323) were studied. They had been identified in a population screening for asthma. A histamine provocation test and PEF variability were assessed over a three-week period. Asthma was defined as signs or symptoms together with a reversible airflow obstruction or BHR to the histamine challenge test. BHR was defined as a PC20 histamine of < or = 8 mg/ml or a PEF variability of > or = 15%. Overall correlation between PC20 and PEF variability was calculated using Spearman's rho. Furthermore, a decision tree was constructed to clarify the role of BHR in diagnosing asthma. RESULTS: Thirty-two patients had a reversibility in forced expiratory volume in 1 second (FEV1) of > or = 9% predicted, 131 patients showed a PC20 of < or = 8 and 11 patients had a PEF variability of > or = 15%. Overall correlation was poor at only -0.27 (P < 0.0001). One hundred and fourteen of the 131 patients diagnosed as having asthma when the histamine challenge test was used were not diagnosed by PEF variability. CONCLUSION: PEF variability cannot replace bronchial provocation testing in assessing BHR. This indicates that PEF variability and bronchial provocation do not measure the same aspects of BHR. If BHR testing is required in diagnosing asthma, a bronchial provocation test has to be used in general practice as well.

Treatment of mild asthma with inhaled corticosteroids: is discontinuation of therapy possible?

BACKGROUND: This study investigated if long-term therapy with inhaled corticosteroids could be discontinued in mild asthma when patients are in a clinically stable phase of the disease. Data were derived from a 2-year randomized, controlled, bronchodilator intervention study in family practice. METHODS: The experimental (stop-steroid) group consisted of 19 asthmatic patients who had used inhaled corticosteroids daily during at least the year preceding this study and who stopped using these drugs because of participation in the bronchodilator intervention study. The control (no-steroid) group consisted of 70 patients with asthma who had not used corticosteroids in the year preceding the study. At the start of the study (8 weeks after stopping steroids), the two groups were completely comparable in all other relevant characteristics. During the 2-year study, patients were treated only with a bronchodilator (salbutamol or ipratropium bromide). Outcome measures were: exacerbations, symptoms, annual decline in forced expiratory volume in 1 second (FEV1), annual change in nonspecific bronchial responsiveness (PC20-histamine), and the need for additional corticosteroid therapy because of symptoms of increased airway obstruction. RESULTS: In the stop-steroid group, 12 of 19 patients (63%) dropped out during the study period because of a deterioration of their clinical condition and need for additional (inhaled) corticosteroid treatment. In the no-steroid group, only eight patients dropped out for this reason (11%). In the stop-steroid group, who did not use steroids for at least 1 year, the annual FEV1 decline was much larger than in the comparison subjects (165 vs 40 ml/yr). CONCLUSIONS: Stopping maintenance treatment with inhaled corticosteroids may not be advisable in all patients with mild asthma. Instead of stopping or interrupting treatment, family physicians are advised to determine the minimal effective daily dose of inhaled corticosteroids for each individual patient that provides adequate control of the disease.

Asthma and chronic bronchitis. Can family physicians predict rates of progression?

OBJECTIVE: To investigate whether the progression rate of asthma or chronic bronchitis can be predicted from a cross-sectional assessment of features that can be measured by family physicians. DESIGN: Secondary analysis of data from a 2-year randomized, controlled bronchodilator intervention study in family practice. SETTING: Twenty-nine general practices in the eastern part of The Netherlands. PATIENTS: One hundred sixty patients (101 with chronic bronchitis, 59 with asthma) from the 29 general practices. INTERVENTIONS: Predictors were related to the annual decline in lung function (the forced expiratory volume in one second) by means of multiple analysis of variance, controlling for age, sex, smoking habits, initial FEV1 level, bronchial hyperresponsiveness, reversibility of obstruction, and medication during the study. MAIN OUTCOME MEASURES: Predictors of the annual decline in lung function (FEV1), which is believed to be the most important measure for progression. RESULTS: Only three variables predicted the decline in lung function: having a barrel-shaped chest, experiencing wheezing, and an unusual diurnal peak-flow rate index. Wheezing was the best predictor of the annual decline in lung function. In chronic bronchitis, the decline in FEV1 of wheezing patients was 133 mL/y compared with 62 mL/y for non-wheezing patients (P < 0.05). In asthma with more severe symptoms, wheezing patients had a tendency to decline 156 mL/y compared with 57 mL/y among non-wheezing patients (P = 0.08). CONCLUSIONS: It is nearly impossible to predict the progression rate of asthma or chronic bronchitis from symptoms, physical signs of the chest, and the PEFR. Therefore, patients with a rapid progression rate can probably be detected only by monitoring progression of the disease through repeated lung function testing.

Periodic treatment regimens with inhaled steroids in asthma or chronic obstructive pulmonary disease. Is it possible?

OBJECTIVE: To determine whether inhaled corticosteroids can be discontinued in the stable phase of asthma or chronic obstructive pulmonary disease (COPD) or if this therapy should be continued. DESIGN: Nonrandomized open uncontrolled 5-year trial. SETTING: Prospective study in general practice. PATIENTS: Forty-eight patients with steroid-dependent asthma or COPD who had shown a decline in forced expiratory volume in 1 second (FEV1) of at least 80 mL per year and at least one exacerbation per year during the first 2 years of bronchodilator treatment. Subjects were treated additionally with inhaled steroids for another 2 years and were finally given the option to stop using steroids. Sixteen patients were willing to stop using beclomethasone and were studied for another year. No recruitment bias took place in this consecutive sample in the fifth year of follow-up. Two of 16 patients developed carcinomas and dropped out. INTERVENTIONS: Two years of bronchodilator treatment alone (400 micrograms of salbutamol or 40 micrograms of ipratropium bromide four times daily), followed by 2 years of additional inhaled corticosteroid treatment (400 micrograms of beclomethasone two times daily), and finally 1 year of bronchodilator treatment alone. MAIN OUTCOME MEASURES: Decline in lung function (FEV1), change in bronchial hyperresponsiveness, indicated by a provocative concentration of histamine causing a 20% fall in FEV1 (PC20), morning peak expiratory flow rate (PEFR), diurnal PEFR, week-to-week variation of PEFR, bronchial symptoms, and exacerbations. RESULTS: The course of FEV1 during the year in which beclomethasone was discontinued was not significantly different when compared with the 2-year period of beclomethasone treatment. Neither did the course of PC20, morning PEFR, diurnal PEFR, symptom score, and exacerbation rate change. Only the week-to-week variation of the PEFR increased after discontinuing steroids. CONCLUSIONS: Discontinuing inhaled steroids is possible in some patients with asthma or COPD after 2 years of regular treatment. This might indicate that for certain groups of patients with mild asthma or COPD, periodic treatment schedules with inhaled steroids is the treatment policy for the future.

Does bronchial hyperresponsiveness precede or follow airway obstruction in asthma or COPD?

OBJECTIVE: The following hypothesis was tested: The degree of bronchial hyperresponsiveness (BHR) is a risk factor for the progression of airway obstruction in asthma, while in chronic obstructive pulmonary disease (COPD) it reflects the existing airway obstruction. METHODS: The relationships between the (annual change in) PC20 histamine and the (annual change in) FEV1 were investigated in a 2-year prospective controlled study. The FEV1 and the PC20 histamine were assessed at 6-month intervals. 183 patients (74 asthma, 109 COPD) participated. The investigated relationships were assessed by means of multiple analysis of variance (ANOVA). Patients used bronchodilator therapy alone. No steroids were permitted during the study. RESULTS: The results demonstrated that the PC20 at the start of the study was related to the subsequent annual decline of FEV1 in asthma (r = 0.32, p < 0.05) but not in COPD (r = -0.10, p = 0.89). Asthmatic patients with a PC20 value < or = 2 mg/ml had an average decline of 118 ml/yr, those with a PC20 value > 2 mg/ml of 27 ml/yr. The change in PC20 histamine during the 2-year study period was related to the annual change in FEV1 in COPD (r = 0.45, p < 0.05), but not in asthma (r = 0.06, p = 0.90). The disturbing influence of possible confounders was investigated and if necessary controlled for. CONCLUSIONS: It was concluded that BHR, assessed with PC20 histamine, is probably involved in the progression of airway obstruction in asthma. In COPD, however, the degree of BHR probably only reflects the degree of existing airway obstruction. This conclusion may contribute to the ongoing debate whether it is useful to combine the diagnosis of asthma, COPD and emphysema under the umbrella-term CARA (or CNSLD = chronic non-specific lung disease). The so-called "Dutch hypothesis" which laid the foundation for this term, suggested that bronchial hyperresponsiveness plays a central role in the pathogenesis of CNSLD. The present study supports evidence that at least BHR does not seem to play the same role in the pathogenesis of asthma and COPD.