Adults with concomitant atopic dermatitis and asthma have more frequent urgent healthcare utilization and less frequent scheduled follow-up visits than adults with atopic dermatitis or asthma only: a nationwide cohort study.

BACKGROUND: Atopic dermatitis (AD) and asthma often co-occur in the same patient, and healthcare utilization is related to disease severity of these diseases. OBJECTIVE: The objective of the study was to investigate differences in healthcare utilization in adults with concomitant AD and asthma compared to patients with asthma or AD only. METHODS: All Danish adults with a hospital diagnosis of AD, asthma or concomitant AD, and asthma recorded in national registries were included. Healthcare utilization data were obtained in 3-month intervals from 2 years prior to index date (the date of the first hospital diagnosis) and to 5 years after. RESULTS: A total of 12 409 patients with AD were included (11 590 with AD only and 819 with concomitant AD and asthma), and 65 539 with asthma only. Adults with concomitant AD and asthma had higher risk of hospitalization for AD (OR 1.38, 95% CI (1.15-1.67), P = 0.001) and asthma (OR 1.16, 95% CI (1.00-1.35), P = 0.047) compared to patients with only AD and asthma, respectively. These patients also had fewer visits in outpatient clinics for AD (OR 0.10, 95% CI (0.08-0.12), P < 0.001) and asthma (OR 0.34, 95% CI (0.29-0.39), P < 0.001) compared to patients with only AD or asthma. Outpatient clinic visits for rhinitis were more frequent among patients with concomitant AD and asthma compared to patients with only AD or asthma. CONCLUSION: Adults with concomitant AD and asthma had different patterns of healthcare utilization compared to adults with AD or asthma alone, suggesting that improvements in management and monitoring may reduce unscheduled healthcare visits and lower healthcare costs.

Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial: Protocol and statistical analysis plan.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of deaths and overburdened healthcare systems worldwide. Systemic low-dose corticosteroids have proven clinical benefit in patients with severe COVID-19. Higher doses of corticosteroids are used in other inflammatory lung diseases and may offer additional clinical benefits in COVID-19. At present, the balance between benefits and harms of higher vs. lower doses of corticosteroids for patients with COVID-19 is unclear. METHODS: The COVID STEROID 2 trial is an investigator-initiated, international, parallel-grouped, blinded, centrally randomised and stratified clinical trial assessing higher (12 mg) vs. lower (6 mg) doses of dexamethasone for adults with COVID-19 and severe hypoxia. We plan to enrol 1,000 patients in Denmark, Sweden, Switzerland and India. The primary outcome is days alive without life support (invasive mechanical ventilation, circulatory support or renal replacement therapy) at day 28. Secondary outcomes include serious adverse reactions at day 28; all-cause mortality at day 28, 90 and 180; days alive without life support at day 90; days alive and out of hospital at day 90; and health-related quality of life at day 180. The primary outcome will be analysed using the Kryger Jensen and Lange test adjusted for stratification variables and reported as adjusted mean differences and median differences. The full statistical analysis plan is outlined in this protocol. DISCUSSION: The COVID STEROID 2 trial will provide evidence on the optimal dosing of systemic corticosteroids for COVID-19 patients with severe hypoxia with important implications for patients, their relatives and society.

Determinants of low risk of asthma exacerbation during pregnancy.

BACKGROUND: Assessment of asthma control every 4-6 weeks during pregnancy is recommended to reduce risk of exacerbation, and by that improve outcome. OBJECTIVE: To identify determinants of pregnancies with low risk of asthma exacerbation. METHODS: All pregnant women enrolled into the Management of Asthma during Pregnancy (MAP) programme at Hvidovre Hospital since 2007. Assessment of asthma control, adjustment of treatment, spirometry and measurement of exhaled nitric oxide (FE NO) were performed, and baseline characteristics and exacerbation history were collected at enrolment. Determinants of low-exacerbation risk pregnancies were identified by logistic regression analysis (stepwise backward elimination). RESULTS: In 1283 pregnancies, 107 exacerbations were observed. Multiple regression analysis revealed that no history of pre-pregnancy exacerbations (P < .001), no prescribed controller medication (P < .001), and clinically stable asthma at enrolment (P = .002) were significantly associated with low risk of exacerbation during pregnancy; with these combined characteristics, only two of 385 pregnancies were complicated by an exacerbation (OR 0.04, 95% CI 0.01-0.18, P < .001). CONCLUSION AND CLINICAL RELEVANCE: Clinically stable asthma at enrolment, together with no history of previous exacerbations and no prescribed controller medication, is a determinant of low risk of an asthma exacerbation during pregnancy, which may guide clinicians in individualizing surveillance of asthma during pregnancy.

Overweight in childhood and adolescence: Does it lead to airway hyperresponsiveness in adulthood?

BACKGROUND: Obesity is increasing worldwide among children and adolescents, and has been associated with an increased incidence of asthma. However, the mechanisms underlying this association are incompletely understood. OBJECTIVE: In this cohort study we aimed to investigate whether being overweight in childhood and adolescence is associated with an increased risk of airway hyperresponsiveness (AHR), a hallmark of asthma, in early adulthood. METHODS: Of 527 subjects from a random population sample of children and adolescents (7-17 years) examined at baseline, a total of 184 subjects completed the follow-up visit 20 years later and were included in the present analysis. Both visits included assessment of height and weight, case history and spirometry. At both visits, bronchial provocation tests were performed using either histamine (baseline) or methacholine (follow-up). In addition, fractional exhaled nitric oxide (FeNO) was measured at follow-up. RESULTS: No significant difference in the prevalence of AHR at follow-up was found between subjects who were overweight or obese at baseline visit (n = 26) (pediatric definition, body mass index ≥ 85%percentile) and normal weight subjects (n = 158) (positive bronchial provocation tests: 15.4% vs. 22.2%, respectively, p = 0.35). Likewise, follow-up FeNO levels did not differ significantly between subjects who were lean and those who were overweight or obese at baseline (geometric mean (95% confidence interval [CI]) 15.1 (13.7, 16.6) parts per billion (ppb) versus 13.0 (10.6, 15.9) ppb, p = 0.23). CONCLUSION: In children and adolescents, being obese or overweight seems not to be associated with an increased risk of AHR or increased FeNO levels in early adulthood.

Exacerbations of asthma during pregnancy: Impact on pregnancy complications and outcome.

Asthma is common among pregnant women, and the incidence of asthma exacerbations during pregnancy is high. This literature review provides an overview of the impact of exacerbations of asthma during pregnancy on pregnancy-related complications. The majority of published retrospective studies reveal that asthma exacerbations during pregnancy increase the risk of pre-eclampsia, gestational diabetes, placental abruption and placenta praevia. Furthermore, these women also have higher risk for breech presentation, haemorrhage, pulmonary embolism, caesarean delivery, maternal admission to the intensive care unit and longer postpartum hospital stay. Asthma has been associated with increased risk of intrauterine growth retardation, small-for-gestational age, low birth weight, infant hypoglycaemia and preterm birth, but more recent prospective studies have not revealed significant associations with regard to these outcomes. In conclusion, asthma exacerbations during pregnancy are associated with complications of pregnancy, labour and delivery. Prevention of exacerbations is essential to reduce the risk of complications and poor outcome.

Add-on montelukast to inhaled corticosteroids protects against excessive airway narrowing.

RATIONALE: Excessive airway narrowing in response to broncho-active stimuli is a predictor for severe exacerbations in asthma. Leukotriene receptor antagonists (LTRAs) have complementary properties to inhaled corticosteroids (ICS) on asthma control. OBJECTIVES: The LTRA montelukast may provide an additional protection against excessive airway narrowing. We tested the add-on effects of montelukast on the maximal response plateau and PD(20) to inhaled methacholine in asthmatics on a stable dose of ICS. METHODS: Thirty-one patients with allergic asthma [14M/17F, 19-50 years, forced expiratory volume in 1 s (FEV(1)) >70% pred., PD(20) <3.9 micromol methacholine], with a twice documented response plateau to methacholine, were randomized in a double-blind (montelukast 10 mg or matching placebo once daily), 12-week parallel study. Bronchoprovocation tests with methacholine (0.03-256 micromol or > or =40% decline in FEV(1)) were repeated every 4 weeks and after wash-out. The main study objectives were changes from baseline in maximal FEV(1) decline at the response plateau (i.e. >2 post-dose FEV(1) values within 5%) and PD(20) to methacholine after 12 weeks' treatment. RESULTS: Neither treatment affected baseline FEV(1) (P=0.62). Compared with placebo, montelukast significantly decreased the maximal response plateau to methacholine (mean difference 9.4%; 95% confidence interval 3.9-15.7; P<0.005), improved the FEV(1) decline (mean change in FEV(1) decline was 2.1% [montelukast] and -0.8% [placebo], respectively, P<0.05), and increased PD(20) methacholine (mean change in PD(20) of 5.3 [montelukast] and 1.4 [placebo] doubling doses, respectively, P<0.001). CONCLUSION: Add-on montelukast to ICS has disease-modifying effects in adults with persistent asthma, and hence reduces the risk of excessive airway narrowing (NCT 00913328).

Prevalence and severity of self-reported asthma in young adults, 1976-2004.

The aim of the present study was to describe the prevalence and severity of asthma in young Danish adults over three decades. Males and females aged 20-35 yrs were sampled from the population of Copenhagen for the three surveys (1976-1978, 1991-1993 and 2001-2004). A total of 3,285 (46% male) subjects answered a questionnaire, and had their height, weight, forced expiratory volume in 1 s (FEV1) and forced vital capacity measured. The prevalence of self-reported asthma was 1.5, 4.7 and 6.9%, respectively, in the three surveys (p<0.001). An increasing prevalence of asthma was observed in both males and females, although it was highest among females. The difference in FEV1 between asthmatic and nonasthmatic subjects gradually increased, being 2.3 (p = 0.56) and 14.2% of the predicted value (p<0.001), respectively, in 1976-1978 and 2001-2004. From the 1991-1994 survey, increasing body mass index, especially >30 kg.m(-2), was associated with a lower percentage predicted FEV1 (p< or =0.005), and further analyses suggested an additive effect of asthma and obesity on FEV1. The proportion of smokers declined from 60 to 38% (p<0.001). The prevalence and severity of asthma have continued to increase over the last three decades among young Danish adults, and the observed increase in severity seems, at least partly, to be related to the increase in prevalence of obesity.

Small intestinal absorption in patients with chronic obstructive pulmonary disease complicated by cor pulmonale - A pilot study.

BACKGROUND: Cor pulmonale is a common complication to Chronic Obstructive Pulmonary Disease (COPD), and may result in increased pressure in the inferior caval vein and stasis of the liver. The chronic pulmonary hypertension may lead to stasis in the veins from the small intestine and thereby compromise absorption of nutrients. AIM: To investigate whether patients with pulmonary hypertension have reduced absorption capacity compared to COPD patients without cor pulmonale. METHODS: Absorption of d-xylose (25 g) and zinc (132 mg), administered as a single dose, was tested in 14 COPD patients, seven with and seven without cor pulmonale. The presence of cor pulmonale was determined by echocardiography. The concentration of d-xylose and zinc were measured in peripheral blood one, two and three hours after ingestion and used as markers of absorption. Furthermore, urine was collected for five hours to determine the amount of excreted d-xylose. RESULTS: No significant difference in absorption of d-xylose (p = 0.28) or zinc (p = 0.51) was found between the two groups. However, a trend towards a delay in d-xylose absorption, as assessed by time-to-peak concentration, was observed in patients with cor pulmonale (p = 0.08). There was no significant difference in the amount of excreted d-xylose in the urine between the groups (p = 0.52). No correlation was found between the tricuspid regurgitation gradient and the absorption of both test-markers (rs = 0.34 and rs = -0.25). Likewise, no correlations were found between the inferior caval pressure during the in- and expiration phases and the absorption of d-xylose (rs = -0.09 rs = 0.23) or zinc (rs = -0.39, rs = -0.39). CONCLUSION: We found no indications that small intestinal absorption is affected in a clinically relevant degree in patients with cor pulmonale.

Findings on the atopic triad from a Danish twin registry.

OBJECTIVE: To estimate to what extent the same genetic and environmental risk factors influence asthma, hay fever and eczema. DESIGN: From the nationwide Danish Twin Registry, twin cohorts born between 1953 and 1982 were contacted for a questionnaire survey, and a total of 29 183 twin individuals (86%) responded. Subjects were classified as cases when responding affirmatively to three questions about the lifetime occurrence of asthma, hay fever and eczema. Variance components twin analysis was conducted using maximum likelihood methods. RESULTS: The phenotypic (within-subject) correlations in liability between the different diseases were 0.57 (95% CI 0.54-0.59) for asthma and hay fever, 0.40 (95% CI 0.36-0.42) for asthma and eczema, and 0.33 (95% CI 0.29-0.36) for hay fever and eczema. Decomposition of these correlations into their genetic and environmental contributions showed that shared genes explained between 70% and 85% of the correlation between the different diseases. The remaining parts were explained by environmental factors shared between the diseases. CONCLUSION: To a large extent, atopic diseases share a common genetic background, although disease-specific genes also play a considerable role. These results can prove informative when counselling families with atopy, and may furthermore be used to guide the search for pleiotropic genes of importance for these diseases.

Mortality and markers of risk of asthma death among 1,075 outpatients with asthma.

BACKGROUND: According to national health statistics, mortality rates for asthma have been increasing steadily over the past decades. Mortality and markers of risk of death from asthma were studied among asthmatics attending a chest clinic in Copenhagen between 1974 and 1990. METHODS: The study group consisted of 1,075 asthmatics in whom the diagnosis of asthma had been verified by objective/paraclinical criteria; they were compared with a sex- and age-matched group of nonasthmatic patients. Both groups of subjects comprised 425 men (mean age, 37.3 years [SD 15.2]) and 650 women (mean age, 38.5 years [SD 16.0]), and the mean follow-up period was 8.6 years (SD 4.2) in both asthmatics and controls. RESULTS: Mortality from all causes was significantly increased in the asthmatic subjects (93 deaths) compared with the control group (41 deaths); relative risk [RR], 2.4; 95% confidence interval [CI], 1.6 to 3.4). The predominant cause of excess mortality was obstructive pulmonary disease, that is, status asthmaticus (14 vs 0 deaths, RR 8.2) and COPD not classified as status asthmaticus (19 vs 0 deaths, RR 8.3). Overall, 91% of the asthmatic cohort survived the mean follow-up period of almost 9 years compared with 96% of the controls. Mortality analysis employing the multiple regression model of Cox revealed that age, pack-years of smoking, eosinophilia, level of FEV1 percent predicted, and degree of reversibility in FEV1 were significant predictors of death from asthma, whereas no association was found between previous hospital admissions for asthma and subsequent death from asthma. In subjects with eosinophil (> 0.45 mia [10(9)/L]), the risk of dying from asthma was 7.4 (CI 2.8 to 19.7) greater than in those without eosinophilia. Compared with subjects with 15 to 24% reversibility in FEV1, the subjects with 25 to 49% and > 50% reversibility had a 2.7 and 7.0 higher risk of death from asthma, respectively. CONCLUSION: Mortality was significantly increased in asthmatics compared with matched controls, primarily because of death from acute and chronic asthma. Furthermore, the present findings suggest that eosinophilia and pronounced increase in FEV1 after bronchodilator are strong markers of subsequent risk of death from asthma.

Longitudinal determinants of bronchial responsiveness to inhaled histamine.

BACKGROUND AND STUDY OBJECTIVE: The point prevalence of bronchial hyperresponsiveness (BHR) is imperfectly associated with current asthma, possibly due to changes over time in bronchial responsiveness (BR). To evaluate cross-sectional and longitudinal determinants of BR, a population sample comprising 408 children and adolescents, aged 7 to 17 years at enrollment, was examined twice, 6 years apart. METHODS: Case history was obtained by interview and questionnaire. BR to inhaled histamine, pulmonary function, and skin prick test reactivity were measured using standard techniques. RESULTS: The point prevalence of BHR (the concentration of histamine causing a 20% decline in FEV1 <8 mg/mL) declined from childhood to early adulthood (25% and 6%, respectively; p<0.001); and similarly a decline in histamine dose-response slope was observed. At both surveys, prechallenge FEV1 percent predicted, asthma, and atopy, especially atopy to house dust mite (HDM), were important determinants for the degree of BR. After adjustment for prechallenge FEV1 percent predicted, no male-female difference was observed in degree of BR. Lower FEV1 percent predicted (p=0.003), asthma (p<0.001), higher degree of BR (p=0.003), and atopy to HDM (p=0.007) at enrollment predicted a higher degree of BR at the second survey (degree of BR at second survey adjusted for prechallenge FEV1). Furthermore, new asthma (p<0.001) and/or atopy to HDM (p=0.003) were associated with higher BR at the second survey. Confining the analysis to nonasthmatics showed that subjects with new or persistent atopy to HDM had significantly increased BR compared with nonatopic subjects; and, moreover, prechallenge FEV1 percent predicted was significantly correlated with BR. CONCLUSIONS: BR declines from childhood to early adulthood, possibly reflecting the increase in airway caliber. The level of FEV1 and atopy, especially to HDM, are important determinants for changes over time in level of BR, also in nonasthmatic subjects.

Long-range correlations of serial FEV1 measurements in emphysematous patients and normal subjects.

In obstructive lung disease the annual change in lung function is usually estimated from serial measurements of forced expiratory volume in 1 s (FEV1). Frequent measurements in each patient may not improve this estimate because data are not statistically independent; i.e., the measurements are autocorrelated. The purpose of this study was to describe the correlation structure in time series of FEV1 measurements. Nineteen patients with severe alpha1-antitrypsin deficiency (phenotype PiZ) and moderate to severe emphysema and two subjects with normal lungs were followed for several years with daily self-administered spirometry. FEV1 measurements fulfilling standard criteria were detrended, and the autocorrelation profile and the power spectrum were calculated. On average the subjects were followed for >3 yr and performed >1,000 acceptable spirometries. The autocorrelation of FEV1 measurements in the emphysematous patients was approximately 0.35 for short intervals and decreased almost exponentially with a half time of 38 days. Between 3 and 4 mo, the autocorrelation function became negative. It reached a minimum of -0.1 at approximately 8 mo and then increased toward zero over the following 12 mo. The autocorrelation function in the two normal subjects showed a similar pattern, but with a faster decay toward zero. In the patients, the power spectrum had a peak at 1 cycle/wk and showed a 1/f pattern, where f is frequency, with a slope of -0.88 at lower frequencies. We conclude that serial spirometric measurements show long-range correlations. The practical implication is that FEV1 need not be measured more often than once every 3 mo in studies of the long-term trends in lung function.

Extrinsic and intrinsic asthma from childhood to adult age: a 10-yr follow-up.

BACKGROUND: Asthma constitutes one of the most common chronic diseases in childhood, yet little is known about the factors that determine the outcome in childhood asthma. The purpose of this study was to describe various factors of potential importance for the outcome in children with intrinsic and extrinsic asthma. METHODS: Of 85 consecutive children, 5-15 years of age with asthma, 70 (82%) participated in a 10-yr follow-up examination. At the time of referral, all children underwent certain tests for asthma (case history, total IgE, skin prick tests, radioallergosorbent (RAST) tests and specific bronchial provocations). On the basis of these tests, 24 children had intrinsic asthma and 46 children had extrinsic asthma. RESULTS: At the follow-up examination, 60 of the 70 adults (86%, 20 with intrinsic asthma) had current symptoms; 54 of the 60(90%; 18 with intrinsic asthma) were receiving maintenance therapy. Both FEV1 %predicted and FEV1/FVC increased significantly (from 73% +/- 19% to 92% +/- 17% and from 75% +/- 13% to 80% +/- 12% respectively) from childhood to early adulthood (P < 0.0001 and P < 0.001), respectively); a matching amelioration of symptoms was observed (P < 0.0001). Adults with current symptoms had a significantly lower FEV1 %predicted at the time of follow-up (90% +/- 2% vs. 100% +/- 4%, P < 0.02) but not in childhood (73% +/- 20% vs. 71% +/- 10%) than adults who had ceased wheezing. CONCLUSIONS: In children with intrinsic asthma, the outcome seems to be predicted by a combination of the initial frequency of symptoms (P = 0.04), initial FEV1 (P = 0.002), active smoking (P = 0.001) and age at onset of respiratory symptoms (P = 0.001), whereas the initial FEV1 (P < 0.001) seems to be a strong predictor for the outcome in children with extrinsic asthma. These findings suggest that the pathogenic mechanisms underlying intrinsic and extrinsic asthma in children may differ.

Risk factors for development of asthma in children and adolescents: findings from a longitudinal population study.

BACKGROUND: The prevalence of asthma appears to be on the increase, and risk factors are not well established. To investigate risk factors for the development of asthma, a population sample of children and adolescents, aged 7-17 years at enrolment, were studied in 1986. Initial examinations were repeated at follow-up in 1992; complete data was available for 408 subjects (199 males). METHODS: Obtained case histories were used to assess the presence of asthma; pulmonary function, skin prick test reactivity, total serum IgE and bronchial responsiveness to inhaled histamine were measured using standard techniques. RESULTS: The 12-month period prevalence of asthma increased significantly from the first to the second examination in both males (P < 0.001) and females (P < 0.001), whereas the number of subjects with a positive histamine challenge test declined in both sexes, although this was only statistically significant in males (P < 0.001). The prevalence of a positive skin prick test was higher at the second examination (26% and 44%, respectively, P < 0.001); the proportion of subjects with a positive skin reaction to house dust mite (HDM pos) increased from 14% to 26%. Bronchial hyper-responsiveness to inhaled histamine (BHR), HDM allergy, a history of wheezy bronchitis and symptoms of asthma at first examination were more prevalent among subjects reporting asthma at the second examination than among subjects without respiratory symptoms. Confining the analysis to subjects without a history of asthma at the first examination showed that asymptomatic BHR ¿Odds ratio [OR] 3.8 [95% confidence interval (CI) 2.5-5.1], P = 0.0002¿, HDM pos [OR 2.6 (95% CI 1.9-3.3), P = 0.005], a history of wheezy bronchitis before the age of 2 years [OR 3.8 (95% CI 2.4-5.2), P = 0.006] and a history of rhinitis and/or eczema [OR 2.8 (95% CI 1.7-3.9), P = 0.007] at first examination were associated with an increased risk for development of symptomatic asthma at some point between the two examinations. No significant relationship could be demonstrated between smoking (passive or active) and the risk for development of asthmatic symptoms. CONCLUSIONS: In conclusion, this longitudinal population study showed an increase in the 12-month period prevalence of asthma with sensitization to HDM and asymptomatic BHR as important risk factors for development of asthma; the temporal relationship between sensitization to HDM and presence of airway abnormalities needs to be explored further.

Office spirometry: temperature conversion of volumes measured by the Vitalograph-R bellows spirometer is not necessary.

The aim of the present study was to investigate the relevance of BTPS (gas at body temperature, atmospheric pressure and saturated with water vapour) conversion of volumes measured with the Vitalograph bellows spirometer. The Vitalograph bellows were tested against a MicroMedical turbine spirometer in extreme temperatures (0-37 degrees C) using a biological control to deliver expired gas at BTPS. Before testing, it was shown that the accuracy of the DairyCard turbine was stable in the relevant temperature range. In a clinical trial six patients with emphysema performed home spirometry b.i.d for 1 month using both the Vitalograph and the turbine. Both the DairyCard and the Vitalograph showed stable accuracy at extreme temperatures when results were reported without any BTPS conversion. These findings were supported by the clinical trial but the conclusions from the clinical setting were weakened by the surprising fact that domiciliary temperatures showed almost no variation. We conclude that the Vitalograph bellows, during dynamic spirometry, measures expired volume at conditions closer to BTPS (than to ATPS) gas at ambient temperature, atmospheric pressure and saturated with water vapour). The use of the BTPS correction based on ambient temperature seems unjustified at office temperatures close to 23 degrees C and at extreme temperatures the conversion of volume will introduce significant over or underestimation.

Patient-administered sequential spirometry in healthy volunteers and patients with alpha 1-antitrypsin deficiency.

The launching of cheap, pocket-sized spirometers, with data storage capability, has made patient-administered sequential spirometry (PASS) an attractive method of monitoring ventilatory capacity. At present, little information is available on the quality of PASS, compared to laboratory spirometry. The aim of this study was to investigate whether patients could perform PASS without loss of reliability and reproducibility as compared with traditional laboratory spirometry. Ten healthy volunteers performed spirometry for 1 month and 10 emphysematous patients with alpha 1-antitrypsin deficiency (type PiZ) performed spirometry twice daily for up to 2 yr. To fulfil Good Clinical Practice criteria on full data documentation, a traditional direct recording spirometer, the Vitalograph R-model, was used. A decompression device was used for calibration and a 3.8% annual drift in volume registration was noted. This drift was largest for the first year. After training, all patients were able to perform unsupervised spirometry, producing technically correct forced expiratory curves. Reproducibility of FEV1 and FVC obtained by PASS was found to be as good as for laboratory spirometry. After adjustment for the diurnal variation, the residual variation of FEV1 was 2.5% (range 1.6-4.2%) for healthy volunteers and 5.6% (range 4.2-7.7%) for emphysematous patients. Forced vital capacity showed the same pattern. In conclusion, PASS is possible in highly motivated individuals without loss of reliability and reproducibility when compared to laboratory spirometry.

Cigarette smoking and asthma.

Cigarette smoking is a well-know health hazard, probably not least for patients suffering from asthma. This review gives a short overview concerning the effects of passive and active smoking on the inception and outcome with regard to longitudinal changes in lung function and mortality for patients with asthma. Substantial evidence suggests that smoking affects asthma adversely. Exposure to environmental tobacco smoke in children, especially maternal smoking, may be a significant risk factor for asthma. Environmental tobacco exposure in patients with established asthma is not only associated with more severe symptoms, but also with lower quality of life, reduced lung function, and increased health care utilisation for asthma, including hospital admissions. Active smoking appears not to be a significant risk factor for asthma, but it is associated with worse outcome with regard to both longitudinal changes in lung function and asthma-related mortality. Based on the current knowledge, it therefore seems of utmost importance to encourage patients with asthma not to smoke. In line with this, patients with asthma should be given full support in their right to a smoke-free environment.

[The effect of salmeterol in the treatment of smokers with chronic obstructive lung disease]. / Effekten af salmeterol i behandlingen af rygere med kronisk obstruktiv lungesygdom.

Patients with chronic obstructive pulmonary disease (COPD) may benefit from long term treatment with bronchodilators despite having a modest acute response to these drugs. To investigate the efficacy of salmeterol in smokers with COPD a double blind, randomised, crossover comparison was performed between salmeterol (50 micrograms twice daily) and placebo in 63 patients with stable COPD (mean age 63 yrs); inclusion criteria: aFEV1) < 60% of predicted and FEV1 reversibility < 15% (0.4 mg salbutamol). Patients received four weeks of therapy with each of the treatment regimens. Assessment of efficacy was done by recording morning and evening peak expiratory flow rates (PEF), respiratory symptoms, and use of rescue salbutamol. Morning PEF values were higher during the salmeterol than during the placebo period, although the mean treatment difference was small (12 l/min (95% confidence limits 6 to 17)). No difference in mean evening PEF values was found. Diurnal variation in PEF was more pronounced during the placebo than during the salmeterol period. Compared with placebo, treatment with salmeterol was associated with lower day time and night time symptom scores and less use of rescue salbutamol both during the day and the night. This study shows that, compared with placebo, treatment with salmeterol produces an improvement in respiratory symptoms and morning PEF values in patients with moderate to severe COPD. Treatment with long acting beta(2)-agonists may therefore result in an improvement in functional status, even in patients suffering from apparently non-reversible obstructive pulmonary disease.

[Eosinophil count in asthma. A marker of disease activity in intrinsic and extrinsic asthma]. / Eosinofiltal ved astma. Markør for sygdomsaktivitet hos patienter med henholdsvis intrinsic og extrinsic astma.

The relationship between eosinophil count and pulmonary function (FEV1), respiratory symptoms, bronchial responsiveness to histamine and diurnal variation in peak expiratory flow rate (PEF) was studied in a group of asthmatics (n = 70) examined in childhood (mean age 10 yrs) and early adulthood (mean age 21 yrs), of whom 24 had intrinsic and 46 extrinsic asthma. Self-reported symptoms of asthma were graded on a scale from zero to five; histamine responsiveness was analysed by means of the dose-response slope (DRS). In both childhood and adulthood, a direct correlation was found between blood eosinophil count and symptom score (r = 0.69, p < 0.001 and r = 0.58, p < 0.001, respectively), whereas inverse correlations were observed between number of eosinophils and FEV1 expressed as percentage of predicted values (r = -0.75, p < 0.001 and r = -0.80, p < 0.001, respectively). Furthermore, in adulthood, eosinophil count was found to be significantly correlated to histamine responsiveness (logDRS) (r = 0.65, p < 0.001) and diurnal PEF variation (r = 0.81, p < 0.001); these correlations were also noted after dividing the subjects into intrinsic and extrinsic asthmatics. The findings in the present study suggest that the peripheral eosinophil count reflects asthmatic activity, and possibly the degree of inflammation in the airways, in both children and young adults.

[Early diagnosis of amiodarone-induced pulmonary toxicity: are repeated lung function tests of any value?]. / Tidlig diagnostik af amiodaroninduceret pulmonal toksicitet: er gentagne lungefunktionsundersøgelser af vaerdi?

Amiodarone therapy for certain life-threatening cardiac arrhythmias is associated with numerous side and adverse effects, of which pulmonary toxicity is one of the most serious adverse reactions. It appears to be generally accepted that amiodarone-induced pulmonary toxicity (APT) is associated with considerable morbidity and mortality. Based on the assumption that detection of APT in an asymptomatic phase would improve the prognosis for these patients, the value of monitoring for toxic effects with various paraclinical tests has been extensively studied. This article summarizes current knowledge of the pulmonary complications of amiodarone therapy with emphasis on the usefulness of pulmonary function tests in the detection of APT. Based on the findings in the published studies, it appears that changes in pulmonary function, including diffusion capacity, over time do not identify patients at risk for development of APT. It is suggested that it is worthwhile to obtain two or three measurements of pulmonary function, including diffusion capacity, within the first few months of therapy in order to establish the variation in the individual patient. When a stable maintenance dose has been reached, subsequent testing should be reserved for patients who develop new or progressive pulmonary symptoms or radiographic infiltrates.