A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences.

Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency=0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P=1.2 × 10(-4)). The variant also confers risk of several serious smoking-related diseases previously shown to be associated with the D398N substitution in CHRNA5. We observed odds ratios (ORs) of 1.7-2.3 for lung cancer (LC; P=4.0 × 10(-4)), chronic obstructive pulmonary disease (COPD; P=9.3 × 10(-4)), peripheral artery disease (PAD; P=0.090) and abdominal aortic aneurysms (AAAs; P=0.12), and the variant associates strongly with the early-onset forms of LC (OR=4.49, P=2.2 × 10(-4)), COPD (OR=3.22, P=2.9 × 10(-4)), PAD (OR=3.47, P=9.2 × 10(-3)) and AAA (OR=6.44, P=6.3 × 10(-3)). Joint analysis of the four smoking-related diseases reveals significant association (P=6.8 × 10(-5)), particularly for early-onset cases (P=2.1 × 10(-7)). Our results are in agreement with functional studies showing that the human α4ß2 isoform of the channel containing R336C has less sensitivity for its agonists than the wild-type form following nicotine incubation.

Combined use of positron emission tomography and volume doubling time in lung cancer screening with low-dose CT scanning.

BACKGROUND: In lung cancer screening the ability to distinguish malignant from benign nodules is a key issue. This study evaluates the ability of positron emission tomography (PET) and volume doubling time (VDT) to discriminate between benign and malignant nodules. METHODS: From the Danish Lung Cancer Screening Trial, participants with indeterminate nodules who were referred for a 3-month rescan were investigated. Resected nodules and indolent nodules (ie, stable for at least 2 years) were included. Between the initial scan and the 3-month rescan, participants were referred for PET. Uptake on PET was categorised as most likely benign to malignant (grades I-IV). VDT was calculated from volume measurements on repeated CT scans using semiautomated pulmonary nodule evaluation software. Receiver operating characteristic (ROC) analyses were used to determine the sensitivity and specificity of PET and VDT. RESULTS: A total of 54 nodules were included. The prevalence of lung cancer was 37%. In the multivariate model both PET (OR 2.63, p<0.01) and VDT (OR 2.69, p<0.01) were associated with lung cancer. The sensitivities and specificities of both PET and VDT were 71% and 91%, respectively. Cut-off points for malignancy were PET>II and VDT<1 year, respectively. Combining PET and VDT resulted in a sensitivity of 90% and a specificity of 82%; ROC cut-off point was either PET or VDT indicating malignancy. CONCLUSION: PET and VDT predict lung cancer independently of each other. The use of both PET and VDT in combination is recommended when screening for lung cancer with low-dose CT.

Lung nodule volumetry: segmentation algorithms within the same software package cannot be used interchangeably.

OBJECTIVE: We examined the reproducibility of lung nodule volumetry software that offers three different volumetry algorithms. METHODS: In a lung cancer screening trial, 188 baseline nodules >5 mm were identified. Including follow-ups, these nodules formed a study-set of 545 nodules. Nodules were independently double read by two readers using commercially available volumetry software. The software offers readers three different analysing algorithms. We compared the inter-observer variability of nodule volumetry when the readers used the same and different algorithms. RESULTS: Both readers were able to correctly segment and measure 72% of nodules. In 80% of these cases, the readers chose the same algorithm. When readers used the same algorithm, exactly the same volume was measured in 50% of readings and a difference of >25% was observed in 4%. When the readers used different algorithms, 83% of measurements showed a difference of >25%. CONCLUSION: Modern volumetric software failed to correctly segment a high number of screen detected nodules. While choosing a different algorithm can yield better segmentation of a lung nodule, reproducibility of volumetric measurements deteriorates substantially when different algorithms were used. It is crucial even in the same software package to choose identical parameters for follow-up.

Effect of CT screening on smoking habits at 1-year follow-up in the Danish Lung Cancer Screening Trial (DLCST).

BACKGROUND: The effect of low-dose CT screening for lung cancer on smoking habits has not been reported in large randomised controlled trials. METHODS: This study evaluated the effect on smoking habits of screening with low-dose CT at 1-year follow up in the Danish Lung Cancer Screening Trial (DLCST), a 5-year randomised controlled trial comprising 4104 subjects; 2052 subjects received annual low-dose CT scan (CT group) and 2052 received no intervention (control group). Participants were healthy current and former smokers (>4 weeks since smoking cessation) with a tobacco consumption of >20 pack years. Smoking habits were determined at baseline and at annual screening. Smoking status was verified using exhaled carbon monoxide levels. Lung function tests, nicotine dependency and motivation to quit smoking were assessed. Quit rates and relapse rates were determined at 1-year follow-up for all subjects. RESULTS: At 1 year the quit rates among smokers were 11.9% in the CT group and 11.8% in the control group (p = 0.95). Relapse rates for former smokers were 10.0% and 10.5% in the CT and control groups, respectively (p = 0.81). Significant predictors (p<0.05) for smoking cessation were: high motivation to quit, low dependency, low ratio of forced expiratory volume in 1 s to forced vital capacity, low pack years, higher age, longer period of abstinence and CT findings necessitating 3-month repeat CT scans. CONCLUSIONS: Overall, quit rates were similar in the CT and control group at 1-year follow-up, with a net quit rate of 6.0%. Quit rates were higher and relapse rate lower among subjects with initial CT findings that necessitated a repeat scan 3 months later.

Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha1-antitrypsin deficiency.

Assessment of emphysema-modifying therapy is difficult, but newer outcome measures offer advantages over traditional methods. The EXAcerbations and Computed Tomography scan as Lung End-points (EXACTLE) trial explored the use of computed tomography (CT) densitometry and exacerbations for the assessment of the therapeutic effect of augmentation therapy in subjects with alpha(1)-antitrypsin (alpha(1)-AT) deficiency. In total, 77 subjects (protease inhibitor type Z) were randomised to weekly infusions of 60 mg x kg(-1) human alpha(1)-AT (Prolastin) or placebo for 2-2.5 yrs. The primary end-point was change in CT lung density, and an exploratory approach was adopted to identify optimal methodology, including two methods of adjustment for lung volume variability and two statistical approaches. Other end-points were exacerbations, health status and physiological indices. CT was more sensitive than other measures of emphysema progression, and the changes in CT and forced expiratory volume in 1 s were correlated. All methods of densitometric analysis concordantly showed a trend suggestive of treatment benefit (p-values for Prolastin versus placebo ranged 0.049-0.084). Exacerbation frequency was unaltered by treatment, but a reduction in exacerbation severity was observed. In patients with alpha(1)-AT deficiency, CT is a more sensitive outcome measure of emphysema-modifying therapy than physiology and health status, and demonstrates a trend of treatment benefit from alpha(1)-AT augmentation.

Quantitative computed tomography: emphysema and airway wall thickness by sex, age and smoking.

We investigated how quantitative high-resolution computed tomography (HRCT) measures of emphysema and airway wall thickness (AWT) vary with sex, age and smoking history. We included 463 chronic obstructive pulmonary disease (COPD) cases and 431 controls. All included subjects were current or ex-smokers aged > or = 40 yrs, and all underwent spirometry and HRCT examination. The HRCT images were quantitatively assessed, providing indices on lung density and airway dimensions. The median (25-75th percentile) %LAA950 (% low-attenuation area < -950 HU) was 8.9 (3-19) and 4.7 (1-16) in male and female COPD cases, respectively, and 0.71 (0.3-1.6) and 0.32 (0.1-0.8) in male and female controls, respectively. %LAA950 was higher in ex-smokers and increased with increasing age and with increasing number of pack-years. The mean+/-SD standardised AWT was 0.504+/-0.030 and 0.474+/-0.031 in male and female COPD cases, respectively, and 0.488+/-0.028 and 0.463+/-0.025 in male and female controls, respectively. AWT decreased with increasing age in cases, and increased with the degree of current smoking in all subjects. We found significant differences in quantitative HRCT measures of emphysema and AWT between varying sex, age and smoking groups of both control and COPD subjects.

Progression of emphysema evaluated by MRI using hyperpolarized (3)He (HP (3)He) measurements in patients with alpha-1-antitrypsin (A1AT) deficiency compared with CT and lung function tests.

BACKGROUND: The progression of emphysema is traditionally measured by pulmonary function test, with forced expiratory volume in 1 s (FEV(1)) being the most accepted and used measurement. However, FEV(1) is insensitive in detecting mild/slow progression of emphysema because of low reproducibility as compared to yearly decline. PURPOSE: To investigate the progression of emphysema over a period of 2 years using diffusion-weighted hyperpolarized (HP) (3)He magnetic resonance imaging (MRI) in patients with alpha-1-antitrypsin (A1AT) deficiency. MATERIAL AND METHODS: Nine patients with severe A1AT deficiency were studied over a period of 2 years (baseline, year 1, and year 2) with HP (3)He MRI using apparent diffusion coefficient (ADC), lung function tests (FEV(1) and carbon monoxide lung diffusion capacity [D(L,CO)]), and computed tomography (CT) using densitometric parameters (15th percentile density [CT-PD15] and relative area of emphysema below -910 HU [CT-RA-910]). RESULTS: Seven patients were scanned three times, one patient two times, and one patient only at baseline. The mean increase in ADC values from first to last HP (3)He MR scanning was 3.8% (0.014 cm(2)/s [SD 0.024 cm(2)/s]; not significant). The time trends for FEV(1), D(L,CO), CT-PD15, and CT-RA-910 were all statistically significant. We found a high correlation between ADC and D(L,CO) (P<0.001). CONCLUSION: This pilot study indicates the possible use of nonionizing HP (3)He MRI for monitoring the progression of emphysema. However, in the future, larger studies are needed to confirm these preliminary results.

Attitudes toward an unsolicited approach in relation to status of genetic disease: exemplified by alpha(1)-antitrypsin deficiency.

Knowledge of a genetic disease in an individual raises the questions of whether and how this information should be communicated to his or her family. The aim of the present study was to provide factual information about attitudes towards an unsolicited approach from a physician regarding genetic counseling within affected families. We performed a questionnaire study among patients with alpha(1)-antitrypsin deficiency, their examined and unexamined relatives, and a control group of Danish citizens. Of 2,146 subjects, the questionnaires were returned by 1,761 (82%), and 1,609 (75%) wanted to participate. Stepwise logistic regression showed that phenotype/subgroup, having descendants, and being female were significantly related to the approval of an unsolicited approach and the informing of relatives. Provided it was difficult for the index case to inform relatives about their risk and about his/her disease, then a total of 75.8% would not proscribe an unsolicited approach by the physician. Most of those for proscribing an unsolicited approach found that relatives should be informed in advance by the index case. The control group of randomly chosen Danes was the most skeptical towards an unsolicited approach. Most individuals found that genetic risk information should be shared with relatives at-risk. A flexible information policy by the health care system based on active approach towards relatives is acceptable to 75 to 95% of individuals in order to ensure diffusion of genetic risk information within families segregating for a genetic disease with a modifiable outcome.

Rheumatoid arthritis cells and biochemical changes in turpentine-induced pleuritis in rabbits.

When turpentine was instilled into the right pleural cavity in rabbits a pleural effusion developed in half of the animals, with a low pH, low glucose concentration, high lactic dehydrogenase activity and the constant presence of rheumatoid arthritis cells in the affected pleural cavity. The biochemical values in the pleural fluid were significantly different from the values for normal pleural fluid obtained by a special microtechnique. These changes resulting from the experimentally induced, simple, irritative turpentine pleuritis are similar to the findings in the pleural effusion in human rheumatoid pleuritis; this implies that such changes are probably non-specific and without evidence of an immunological background.

Repeatability of lung density measurements with low-dose computed tomography in subjects with alpha-1-antitrypsin deficiency-associated emphysema.

RATIONALE AND OBJECTIVES: Multislice computed tomography (MSCT) of the lungs provides a new opportunity for longitudinal assessment of lung densities because of shorter scan duration. The aim of the present study was to assess the intraindividual variation of lung densities measured by MSCT of patients with emphysema. METHODS: Ten patients with emphysema participated in a study in which MSCT was obtained on two occasions, approximately 2 weeks apart. Scanning parameters were 140 kV, 20 mAs, 4 x 2.5-mm collimation, and effective slice thickness of 2.5 mm. Lung density was measured as the 15th percentile point and the relative area below -910 Hounsfield units (HU) by using Pulmo-LKEB software. RESULTS: The mean difference of the 15th percentile point was -1.29 +/- 3.2 HU, and that for the relative area below the -910-HU parameter was -1.02% +/- 3.09%. Intraclass coefficients of variation were 0.96 (0.86-0.99) and 0.94 (0.8-0.98), respectively (95% confidence interval). CONCLUSIONS: Lung density parameters of emphysema derived by MSCT provide an opportunity for analysis of the treatment effects of new drugs on the progression of emphysema.

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.

A dominant Mycobacterium tuberculosis strain emerging in Denmark.

SETTING: Denmark, a high-income country with a low prevalence of tuberculosis. OBJECTIVE AND DESIGN: Molecular epidemiological studies of Mycobacterium tuberculosis strains are conducted worldwide, and distinct strains have been associated with large outbreaks of tuberculosis. This is the first systematic population-based search for distinct strains of M. tuberculosis in Denmark among 4102 strains DNA fingerprinted nationwide from 1992 to 2001. RESULTS: A specific strain of M. tuberculosis has emerged rapidly in Denmark: in 1992, the Danish Cluster 2 strain accounted for 5.8% of all culture-positive Danish-born cases, increasing to 29.0% in 2001. The Cluster 2 cases were on average younger (41.8 vs. 51.4 years), more likely to be male (81.4% vs. 64.1%), and more likely to have pulmonary involvement only (90.3% vs. 64.6%) than other Danish-born cases. During the first 4 observation years, they were mainly found in the capital city, Copenhagen, but were later increasingly observed in the provinces. CONCLUSION: The reasons for the increasing dominance and change in geographical distribution of Cluster 2 strains in Denmark is unknown, but may be partly explained by the fact that Cluster 2 is associated with younger males with pulmonary disease manifestation. We consider it as an outbreak and believe the situation requires increased focus on early tuberculosis diagnosis and control of transmission in Denmark.

Spontaneous changes in bronchial responsiveness in children and adolescents: an 18-month follow-up.

The purpose of this study was to investigate spontaneous changes in bronchial responsiveness to inhaled histamine over a period of 18 months. The first measurements in 495 subjects, 7 to 16 years of age, were made in 1986. Bronchial hyperresponsiveness (BHR), i.e., PC-20 FEV1 less than or equal to 8.0 mg/mL, was found in 79 (16%) individuals, of whom 28 (35%) had symptoms of asthma. Twenty asthmatic and 42 non-asthmatic subjects who had BHR (78%) were re-examined 18 months later. The asthmatics had a modest change in BHR, while in the non-asthmatics bronchial response to inhaled histamine and exercise was significantly decreased. In twenty-two subjects (36%) bronchial response was within the normal range; of these 18 were non-asthmatic. Six asthmatics (30%) and two non-asthmatics (5%) had an increased BHR at follow-up. Two subjects (5%) developed symptoms of asthma by the time of follow-up, with an unchanged degree of BHR. Sex, age, atopic symptoms, and viral respiratory infections at the first examination were unrelated to changes in bronchial responsiveness. However, changes of BHR in the non-asthmatic subjects were significantly correlated to changes in bronchial response to exercise. Although spontaneous changes in bronchial responsiveness occur in asthmatic, as well as non-asthmatic subjects, asthmatics persistently have hyperresponsive airways. Development of asthma was found to occur among subjects with persistent BHR.

The effect of inhaled glucocorticosteroids in emphysema due to alpha1-antitrypsin deficiency.

Despite the success of inhaled steroids in controlling asthma, the benefit in patients with chronic obstructive pulmonary disease (COPD) remains controversial. Five subjects with moderate to severe emphysema due to alpha 1-antitrypsin deficiency (phenotype PiZ) were followed with daily home spirometry in a 2 x 8 weeks, randomized double-blind, placebo-controlled, crossover study of inhaled budesonide 0.8 mg b.i.d. In three of the five patients, there was a statistically significant increase in the mean forced expiratory volume in 1 s (FEV1), and in two of these patients, there was also a statistically significant increase in the mean forced vital capacity (FVC) during budesonide treatment. A significant diurnal variation in FEV1 and FVC was found in three and two patients, respectively, but did not change significantly during treatment. These findings emphasize the need for renewed evaluation of inhaled steroids in the treatment of patients with emphysema, and indicate that individual patients may have significant clinical improvement.

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.

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.

Classification of pulmonary lesions into central and peripheral with a template applied on chest X-ray.

To facilitate the understanding of the anatomical localization of pulmonary lesions and to optimize diagnostic evaluation, a template was designed which, on conventional chest X-rays, could be employed to discriminate between central and peripheral pulmonary lesions. The term 'central' implies that the lesion should be visible in the tracheobronchial tree through a fibre-optic bronchoscope, and the term 'peripheral' suggests that the lesion is not visible through a bronchoscope. In 20 patients examined by fibre-optic bronchoscopy, the bronchoscope was wedged into four pre-selected segmental bronchi in each lung. Using fluoroscopy, the tip of the bronchoscope was marked out on the skin with leadshot. On subsequent chest X-rays, with posterior-anterior and right lateral views, the distances and angles of the markings of the bronchi were mapped out in relation to the main carina. These data were used to design the template.

Secular trends of allergic asthma in Danish adults. The Copenhagen Allergy Study.

Numerous studies have reported increases in asthma prevalence among children world-wide. Less is known about similar trends in adults. We aimed to investigate whether the prevalence of allergic asthma symptoms had increased in an adult general population. Two cross-sectional surveys using identical methods were carried out in 1989 and 1998. A one-page questionnaire on respiratory symptoms was mailed to random samples of 15-41-year-olds living in Copenhagen. The response rates were 86.6% (3624/4185) and 78.8% (2402/3048) in 1989 and 1998, respectively. The questionnaire was validated with specific immunoglobilin E (IgE) positivity as the reference in a random sample of responders in connection with both surveys. We found a significantly increased prevalence of subjects who reported shortness of breath on exposure to pollens (6.6% 0 s. 10.3%, odds ratio 1.61, 95% CI 1.34-1.95), furry animals (5.4% vs. 7.6%, odds ratio 1.45, 95% CI 1.17-1.79), and house dust (7.8% vs. 10.2%, odds ratio 1.35, 95% CI 1.12-1.61). The validation of these symptoms showed that the positive predictive values were reasonably stable over time, which may support that a true increase in allergic asthma has occurred. In conclusion, the prevalence of allergic asthma symptoms increased significantly in this adult general population over a 9-year period.

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.