Three phenotypes of adult-onset asthma.

RATIONALE: Adult-onset asthma differs from childhood-onset asthma in many respects. It is more heterogeneous, often severe and frequently associated with loss of lung function. To identify underlying mechanisms of adult-onset asthma and to capture predictors of disease progression, detailed characterization and phenotyping is necessary. OBJECTIVES: To characterize adult-onset asthma and identify subphenotypes of adult-onset asthma. METHODS: A cohort of 200 patients with adult-onset (>18 year) asthma (age 54 (26-75) year) was recruited from one academic and three nonacademic pulmonary outpatient clinics in Amsterdam, the Netherlands. These patients were fully characterized with respect to clinical, functional and inflammatory markers. After data reduction, K-means nonhierarchical cluster analysis was performed to identify clusters of adult-onset asthma. MEASUREMENTS AND MAIN RESULTS: Patients with adult-onset asthma were predominately female (61%) and nonatopic (55%). Within this group of patients were identified three clusters of adult-onset asthma. Cluster 1 (n = 69) consisted of patients with severe eosinophilic inflammation-predominant asthma and persistent airflow limitation despite high-intensity anti-inflammatory treatment, with relatively low symptom scores. The second cluster was characterized by obese women with frequent symptoms, high healthcare utilization and low sputum eosinophils. The third cluster consisted of patients with mild-to-moderate, well-controlled asthma with normal lung function and low inflammatory markers. Repeatability accuracy was 98.2%. CONCLUSIONS: Amongst patients with adult-onset asthma, three subphenotypes can be identified with distinct clinical and inflammatory characteristics. These subphenotypes help to understand the underlying pathobiology and provide clinicians with directions for personalized management.

[The practice guideline 'Smoking cessation' from the Dutch College of General Practitioners; a response from the perspective of pulmonary medicine]. / De standaard 'stoppen met roken' van her Nederlands Huisartsen Genootschap; reactie vanuit de longgeneeskunde.

The practice guideline 'Smoking cessation' from the Dutch College of General Practitioners has been published. If general practitioners are going to use the standard, this can have a great impact on smoking in the Dutch population. A decrease in smokers among the population will also have an impact on several smoking-related chronic diseases from a preventive point of view. The guideline emphasizes that smoking cessation is not a one-stop shop but that it requires a long-term effort.

[The practice guideline: 'Treatment of tobacco dependence']. / Richtlijn 'Behandeling van tabaksverslaving'.

The interdisciplinary guideline 'Treatment of tobacco dependence' discusses the approach to smoking patients. The point of departure is the concept that smoking is an addiction and that its treatment should be based on this fact. The effectiveness of treatment depends on the patient's motivation to stop smoking and on the intensity of the intervention. Pharmacotherapy may be of added value here, particularly for persistent smokers. The guideline aims at reaching as many smoking patients as possible, regardless of whether there is a relationship between their symptoms or ill health and smoking. Practitioners should ask about smoking habits regularly and smokers should be advised at least once to stop. Further treatment and guidance aims in particular to increase the motivation to quit and at those who are prepared to stop on the basis of the stages-of-change model. More intensive possibilities for treatment, by both general practitioners and specialists, are needed for persistent smokers. Such facilities are hardly available at all in The Netherlands at present, but will have to be developed to make the cost-effective treatment of tobacco addiction possible on a large scale.

A multicentre, randomized, double-blind, placebo-controlled, 1-year study of bupropion SR for smoking cessation.

BACKGROUND: Bupropion sustained release (bupropion SR) has been shown to increase smoking cessation success rates in the US studies. OBJECTIVE: To determine whether bupropion SR, in combination with counselling, is effective for smoking cessation in a multi-country study. METHODS: This randomized, double-blind, placebo-controlled trial enrolled 707 smokers. A total of 527 received bupropion SR 300 mg daily for 7 weeks and 180 received placebo. A total of 11 clinic visits and 10 telephone contacts were scheduled, during the course of 1 year. Seven-week and 12-month abstinence rates were the study outcomes. RESULTS: Both continuous and weekly point prevalence smoking abstinence rates were significantly higher in the bupropion SR group compared with placebo. The continuous abstinence rate from weeks 4 to 7 was 46% in the bupropion SR group compared with 23% in the placebo group [odds ratio (OR) = 2.82; 95% confidence interval (CI) 1.89-4.28; P < 0.001). At month 12, the continuous abstinence rates were 21% for the bupropion SR group and 11% for the placebo group (OR = 2.19; 95% CI 1.29-3.86, P = 0.002). For most nicotine-withdrawal symptoms small changes were measured. Adverse events were higher for the bupropion SR group compared with placebo (insomnia 24% vs. 15%; dry mouth 13% vs. 5%). CONCLUSION: Bupropion SR in combination with counselling increased the abstinence rate compared with placebo, and was well tolerated.

Bupropion SR for smoking cessation in smokers with cardiovascular disease: a multicentre, randomised study.

AIMS: To investigate the safety and efficacy of bupropion sustained release (bupropion SR) in promoting abstinence from smoking in subjects with cardiovascular disease (CVD). METHODS: Six hundred twenty-nine subjects with CVD who smoked >/=10 cigarettes/day were randomised in a double-blind, multicentre study to receive bupropion SR (150 mg twice daily) or placebo for 7 weeks, with a follow-up of 52 weeks. Primary efficacy endpoint: continuous abstinence from smoking from weeks 4 to 7. Secondary endpoints: continuous abstinence (weeks 4-12, 4-26 and 4-52) and weekly point prevalence abstinence. All participants received brief motivational support. Safety was evaluated throughout the study. RESULTS: Continuous smoking abstinence rates from weeks 4 to 7 were significantly higher in subjects receiving bupropion SR compared with placebo (43 vs. 19%, odds ratio [OR]=3.27, 95% confidence interval [CI] 2.24-4.84; P<0.001). Continuous abstinence rates from weeks 4 to 26 and 4 to 52 continued to be more than double for bupropion SR compared with placebo (27 vs. 11%; 22 vs. 9%, P<0.001). Weekly point prevalence abstinence was significantly higher for participants who received bupropion SR compared with placebo at weeks 3, 7, 26 and 52 (P<0.001). In both groups, there were no clinically significant changes in blood pressure and heart rate throughout the treatment phase. Overall, 6% of the participants (n=36) discontinued study medication due to an adverse event (bupropion SR, n=17; placebo, n=19). CONCLUSIONS: After 7 weeks of bupropion SR treatment, more than twice as many smokers with CVD had quit smoking at 1 year compared with placebo. The safety profile of bupropion SR was similar to that previously observed in general smoking populations.

Smoking cessation: which aids are worthwhile?

Smoking is a major preventable health risk in western society. In the Netherlands, it is held responsible for 86 and 36% of annual mortality from lung cancer and cardiovascular disease, respectively. Nevertheless about 33% of Dutch people smoke. Only 2% of smokers quit successfully after being advised to stop once by a physician. Although the medical profession should play a leading role in campaigns to stop smoking, general practitioners advise only 10% of their smokers to quit. An overview was made of the various aids that can be used to support attempts to quit smoking. Three aids: supportive schedules, nicotine replacement and bupropion chloride had proven long-term effectiveness in up to 5-10, 3-13 and 11-15% of the subjects, respectively. In conclusion, supportive counselling combined with nicotine substitutes or bupropion chloride is the most worthwhile intervention to support quitting attempts. Wider application of this strategy is expected to have major implications on morbidity (50% myocardial infarct risk reduction) and mortality in the Netherlands.

[Bupropion: an effective new aid for smoking cessation]. / Bupropion: een effectief nieuw hulpmiddel bij het stoppen met roken.

Smoking is responsible for a substantial percentage of the total morbidity and mortality in western society. In the Netherlands 34% of the population smoke. A considerable part of the smokers tried to stop smoking, but did not succeed. Since December 1999 a new type of anti-smoke therapy is available; bupropion chloride (Zyban). With this treatment an improvement in success ratio in comparison with placebo is described of 11-15% after a year in a healthy population. Combined with nicotine patches this percentage was 20%. These percentages are higher than those of nicotine replacement therapy alone (3-13%). It is very important that effects of bupropion are tested in high-risk patients with asthma, chronic obstructive pulmonary disease (COPD) and cardiovascular diseases as these groups may benefit most from cessation of smoking. Especially in the COPD group cessation of smoking makes a more substantial contribution to improvement of the disease process than the medication now available. Therefore, it might be considered to prescribe bupropion under strict control in this group even now, before definitive research results are obtained.

Double-blind placebo-controlled study of the hyperventilation provocation test and the validity of the hyperventilation syndrome.

BACKGROUND: Hyperventilation syndrome (HVS) describes a set of somatic and psychological symptoms thought to result from episodic or chronic hyperventilation. Recognition of symptoms during the hyperventilation provocation test (HVPT) is the most widely used criterion for diagnosis of HVS. We have investigated the validity of the HVPT and of the concept of HVS. METHODS: In a randomised, double-blind, crossover design, the ability of 115 patients with suspected HVS to recognise symptoms during the HVPT was compared with the ability to recognise symptoms during a placebo test (isocapnic overbreathing, with carbon dioxide levels maintained by manual titration). 30 patients who had positive results on the HVPT underwent ambulatory transcutaneous monitoring of pCO2 to ascertain whether they hyperventilated during spontaneous symptom attacks. FINDINGS: Of the 115 patients who underwent the HVPT and the placebo test, 85 (74%) reported symptom recognition during the HVPT (positive diagnosis HVS). Of that subset, 56 were also positive on the placebo test (false-positive), and 29 were negative on the placebo test (true-positive). False-positive and true-positive patients did not differ in symptom profile or in physiological variables. During ambulatory monitoring (15 true-positive, 15 false-positive) 22 attacks were registered. Transcutaneous end-tidal, pCO2 decreased during only seven. The decreases were slight and apparently followed the onset of the attack, which suggests that hyperventilation is a consequence rather than a cause of the attack. There were no apparent differences between false-positive and true-positive patients. INTERPRETATION: The HVPT is invalid as a diagnostic test for HVS. Hyperventilation seems a negligible factor in the experience of spontaneous symptoms. The term HVS should be avoided.

Sarcoidosis accompanied by pulmonary tuberculosis and complicated by sacroiliitis.

We report the unique occurrence of a unilateral sacroiliitis in a patient with active sarcoidosis accompanied by pulmonary tuberculosis. Convincing (clinical) evidence of sarcoidosis as the extremely rare cause of this articular involvement is presented. Discussion is focused on comparison of sarcoidosis and tuberculosis, particularly with respect to their articular involvement, and the literature of previously reported cases of sarcoid sacroiliitis is briefly reviewed.