Twelve-year longitudinal study of respiratory status in dairy farmers.

To evaluate respiratory risk in dairy farmers, the present authors conducted a longitudinal study in the Doubs region of France. From a cohort constituted in 1986 (T1), 157 (62.8%) dairy farmers and 159 (63.6%) controls were re-evaluated in 1998 (T3). The study protocol comprised a medical and occupational questionnaire, spirometric tests at both evaluations, and noninvasive measure of blood oxygen saturation with pulse oximetry (S(p,O(2))) at T3. In 1998, the prevalence of chronic bronchitis was higher in dairy farmers. In cross-sectional analyses, all respiratory function parameters and S(p,O(2)) were significantly lower in dairy farmers. In a multiple linear regression model, farming, age, male sex and smoking were significantly and negatively correlated with S(p,O(2)). However, the mean annual decline in respiratory function parameters did not differ significantly between groups. After adjustment of covariables, accelerated decline in vital capacity and forced expiratory volume in one second was associated with age, smoking and male sex. Decline in vital capacity was accelerated in dairy farmers working in traditional farms and those currently foddering. The current study demonstrates that dairy farming is associated with an increased risk of lung disorders and a decrease in blood oxygen saturation and suggests that respiratory function impairment is correlated with cumulated exposure to organic dusts.     

Lung status in young Danish rurals: the effect of farming exposure on asthma-like symptoms and lung function.

The aim of this study was to assess the prevalence of asthma (self-reported) and relate this to lung function and factors associated with asthma in young farmers. Two hundred and ten female and 1,691 male farming students together with 407 males controls were studied. Each subject underwent a medical interview; forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were recorded using a dry wedge spirometer. Histamine bronchial reactivity was measured using the Yan method. Skin prick testing was performed using inhalant allergens. Nonsmokers had lower prevalence of asthma (5.4-10.8%) than smokers (11.3-21.0%) (p<0.05). Females reported symptoms of asthma nearly twice as often as males. Sex, smoking and a family history of asthma/allergy were significantly associated with asthma. Controls had higher standardized FEV1 and FVC residuals than male students, both nonsmokers (0.21 and 0.24) versus (-0.06 and -0.05) and smokers (0.29 and 0.33) versus (-0.11 and 0.13) (p<0.032). Bronchial hyperresponsiveness, asthma, siblings with allergy and working with cattle (controls only) were significantly associated with reduced lung function. In conclusion, the prevalence of asthma was significantly related to smoking, female sex, family history of asthma and allergy. Whilst bronchial hyperresponsiveness was associated with reduced lung function and lung function was slightly reduced in the male farming students, there was no association found between occupational farming exposure and either lung symptoms or lung function.     

Working in swine-confinement buildings causes an accelerated decline in FEV1: a 7-yr follow-up of Danish farmers.

Work in swine confinement units causes exposure to high levels of organic dust and is associated with a high prevalence of work-related respiratory symptoms and probably with accelerated decline in forced expiratory volume in one second (FEV1). A 7-yr follow-up on FEV1, forced vital capacity (FVC), bronchial reactivity, and respiratory symptoms was performed on 181 Danish farmers. The participation rate was 76.3% and nonparticipants had more symptoms, were more likely to be current-smokers and had lower lung function in the first survey than participants in both surveys. Farmers who worked exclusively with pigs in the follow-up had an accelerated decline in FEV1 but not in FVC compared with dairy farmers, where the observed decline in FEV1 was close to the expected. For a nonsmoking pig farmer compared to a nonsmoking dairy farmer the mean additional decline in FEV1 was 17 mL x yr(-1) (53.0 mL x yr(-1) versus 36.1 mL x yr(-1)). The authors conclude that working in swine confinement units causes an accelerated decline in forced expiratory volume in one second but not in forced vital capacity. The mean decline is approximately 0.5 L during a working life and some farmers will develop clinically significant airway obstruction due to work in swine confinement units.     

Respiratory function after esophagectomy for patients with esophageal cancer

BACKGROUND/AIMS: Postoperative respiratory hypofunction sometime ruins quality of life of patients with esophageal cancer. From 1993, we introduced transhiatal esophagectomy without thoracotomy as a less invasive surgery to prevent postoperative respiratory complications for patients who have relatively early stage of esophageal cancer and have preoperative respiratory complication, or who are older in age. In this study, postoperative long-term evaluation of respiratory functions of patients with esophageal cancer who underwent esophagectomy was performed. METHODOLOGY: Among the patients with esophageal cancer who underwent esophagectomy in our hospital between 1993 and 1995, we selected 13 patients who underwent transhiatal esophagectomy (transhiatal group) and 9 patients who underwent transthoracic esophagectomy (transthoracic group). Conventional respiratory function tests (VC, vital capacity; FVC, forced vital capacity; FEV1, forced expiratory volume in 1 second; FEV1/FVC, ratio of FEV1 to FVC; PEF, peak expiratory flow) were compared between the two groups at 3, 6, and 12 months after operation. RESULTS: In the transhiatal group, postoperative average values of VC, FVC, and FEV1 recovered 92%, 98%, and 93% of preoperative average values at 6 months after operation, while in the transthoracic group, the average values of VC, FVC, and FEV1 were still 78%, 78%, and 72% of preoperative average values at 6 months after operation. Postoperative respiratory complications were detected in 4 patients (transhiatal: 2 and transthoracic: 2). The recovery rates of VC, FVC, FEV1, FEV1/FVC, and PEF at 6 months after operation of these 4 patients were not different from those of 18 patients without postoperative respiratory complications. CONCLUSIONS: In patients treated with transthoracic esophagectomy, postoperative respiratory hypofunctions continued over 6 months after surgery. However, postoperative respiratory complications may not be related with the long-term postoperative respiratory hypofunction in patients with esophageal cancer.     

Is respiratory mucus hypersecretion really an innocent disorder? A 22-year mortality survey of 1,061 working men

The relation of chronic air-flow limitation and respiratory mucus hypersecretion to all causes of mortality was studied in a population of 1,061 men working in the Paris area, surveyed initially in 1960/1961, and followed for 22 yr. During this period, 369 deaths occurred; VC, FEV1, FEV1/H3, and FEV1/VC were significantly associated with mortality, even when age, smoking, occupational dust exposure, and chronic phlegm were taken into account. Besides the obstructive disorder, the hypersecretory disorder (chronic phlegm) was significantly associated with mortality. Controlling, using Cox's model, for age, FEV1/H3, smoking habits, and dust exposure, all factors associated with chronic mucus hypersecretion and mortality, showed that phlegm production remained significantly related to death (relative risk, = 1.35; p less than 0.01). Although relatively weak, this relationship is not negligible in terms of public health because of the high prevalence of chronic phlegm.     

The effects of Aspergillus fumigatus challenge on exhaled and nasal NO levels.

Several studies have previously shown that exposure to indoor air microbes from moisture-damaged buildings can cause adverse health effects. Aspergillus fumigatus is one of the best-documented moulds causing health problems to those exposed. In this study, inhalation of a commercial A. fumigatus solution was assessed, to establish if it would have effects on fractional exhaled (FeNO) and nasal (FnNO) nitric oxide levels and on lung function. The results were compared with placebo challenge. A total of 28 subjects were divided into three study groups: group 1 had been exposed to occupational mould; group 2 consisted of atopic subjects; and group 3 was a control group. Some 3 h after A. fumigatus challenge, there was a considerable increase in FeNO, and a significant difference was observed between the A. fumigatus and placebo inhalations. The difference was seen in all study groups. No such differences were found in the levels of FnNO or nitrite in nasal lavage fluid. Subjects reported significantly more frequent respiratory tract symptoms after the A. fumigatus inhalation compared with placebo challenge. In conclusion, it was shown here that inhalation challenge of Aspergillus fumigatus elevated fractional exhaled nitric oxide levels. An increase in fractional exhaled nitric oxide may serve as an indicator of respiratory inflammation of acute mould exposure.     

Respiratory function in children undergoing bone marrow transplantation.

We conducted a prospective study of respiratory function in children undergoing bone marrow transplantation (BMT) for onco-hematological disorders. Each child was evaluated before and 100 days after BMT. The investigations included clinical examination, chest X-ray, and pulmonary function tests (PFT) to determine: slow vital capacity (VC), functional residual capacity (FRC), total lung capacity (TLC), forced expiratory volume in 1 s (FEV1), carbon monoxide diffusing capacity (DLCO), ratio of residual volume (RV) to TLC, and FEV1/VC. The values obtained before and after BMT were compared to predicted values, and the post-BMT values were compared to the pre-BMT values (Student's t-test). From 1986 to 1995, 77 children underwent BMT, of whom 39 were available for testing. The pre-BMT VC (P = 0.0234) and DLCO (P < 0.0001) were lower and FRC higher (P < 0.0001) than predicted values. After BMT, the VC (P = 0.004), TLC (P = 0.044), and FEV1 (P = 0.012) were lower, and the RV/TLC ratio was higher (P = 0.043), compared with pre-BMT data. The observed respiratory abnormalities were not clinically relevant. The only identifiable risk factor for a decrease in lung function was age at BMT. This study shows that some lung dysfunction may be present before BMT and be further altered by BMT. This stresses the need for longitudinal respiratory monitoring and follow up to detect such dysfunctions and to insure an optimal treatment program for these children.     

Prevalence of chronic bronchitis and respiratory function in a group of dairy farmers in the French Doubs province

We used a questionnaire combined with medical history and spirometric studies to compare symptoms and respiratory function in two groups of subjects living in the French province of Doubs. A group of 250 dairy farmers was compared with 250 control subjects, matched with regard to sex, age, height, and smoking habits. The prevalence of acute bronchial infections and dyspnea was identical in the two groups. Among dairy farmers, 30 (12 percent) had chronic bronchitis vs 15 (6 percent) in the control group (p less than 0.05). Chronic bronchitis was more common in patients aged over 40 years (p less than 0.001) and in nonsmokers (p less than 0.001). All respiratory function parameters measured (expressed as a mean percentage of values measured in comparison with theoretic values) were lower in the dairy farmer group than in the control group. With regard to degree of bronchial obstruction, the difference between the two groups was more marked in patients aged 40 years and over and in nonsmokers. Dairy farmers' occupation is a risk factor of chronic bronchitis and bronchial obstruction, in particular in patients aged 40 years and over and in nonsmokers.     

Effect of allergic bronchopulmonary aspergillosis on lung function in children with cystic fibrosis

RATIONALE: The relationship between sensitization to Aspergillus fumigatus and progression of pulmonary function is not yet established in cystic fibrosis (CF). OBJECTIVES: We aimed to evaluate onset of A. fumigatus sensitization and development of allergic bronchopulmonary aspergillosis (ABPA), as well as to determine the physiologic factors of lung function influencing these mechanisms in CF. METHODS: Serial annual lung function tests performed in 122 children with CF (62 males; 60 females; age: 6-18 yr) provided data pertaining to FRC measured by plethysmography, lung clearance index, volume of trapped gas, effective specific airway resistance, and forced expiratory indices (FEV1, FEF at 50% VC). Specific IgE to recombinant A. fumigatus allergens, rAspf1 and rAspf3, served as marker for sensitization, and to rAspf4 and rAspf6 as indications for a serologic ABPA, were clinically diagnosed (Nelson criteria). By linear mixed-effect model analysis, five patient groups, (1) not sensitized and free from Pseudomonas aeruginosa, (2) intermittently P. aeruginosa colonized, (3) chronically P. aeruginosa infected, (4) sensitized, and (5) with ABPA, were retrospectively evaluated. MEASUREMENTS AND MAIN RESULTS: A. fumigatus sensitization was best reflected by increased rAspf1+3-specific IgE levels, whereas, in most patients, sensitization was preceded by P. aeruginosa infection. Patients with ABPA demonstrated the most severe progression in all lung function parameters, and FEF at 50% VC, volume of trapped gas, and effective specific airway resistance were the best predictors (p < 0.0001). However, regarding distinction between sensitization to A. fumigatus and development of ABPA in the course of CF, chronic P. aeruginosa infection has to be taken into account. CONCLUSIONS: Airway narrowing, gas trapping, and small airway disease are the major targets for functional derangement in ABPA.     

Lung health in Alberta farmers.

SETTING: A study conducted in the rural areas of two counties in east-central Alberta, Canada. OBJECTIVE: To investigate the relationship between lung health and dust exposure in farmers. DESIGN: A cross-sectional study of 781 farmers growing grain crops and raising livestock. Measurements included a questionnaire on respiratory symptoms, smoking habits and occupation, skin prick tests using common aeroallergens, and spirometry. RESULTS: Immediate skin reactivity to common aeroallergens was less prevalent in farmers with higher reported intensity of dust exposure. Respiratory symptoms suggestive of bronchitis had a significant dose-response relationship with the reported intensity of dust exposure. Respiratory symptoms consistent with bronchial responsiveness were significantly positively associated with cumulative dust exposure. There was a significant positive association between a physician's diagnosis of bronchitis and intensity of dust exposure. FEV1 and FEV1/FVC were significantly negatively associated with cumulative dust exposure. Ten years of exposure to a moderate dust level was associated with a deficit of 43 ml in the FEV1 and a deficit of 0.44% in the FEV1/FVC. CONCLUSIONS: Despite evidence of worker selection related to dust exposure, these farmers experienced respiratory symptoms, respiratory conditions, and reduced lung function associated with reported occupational dust exposure.     

Factors effecting impact of Aspergillus fumigatus sensitization in cystic fibrosis

The clinical impact of Aspergillus fumigatus (Af) sensitization in cystic fibrosis (CF) is controversial. We examined the effect of Af sensitization (Afs) on pulmonary function and growth using a retrospective cohort analysis over two 5-year study periods: 1996-2000 (19 Afs cases and 19 controls) and 2001-2005 (24 Afs cases and 23 controls). Sensitization was defined as Af specific radioallergosorbent test (RAST) >or= 17.5 iu/ml and total serum IgE level >or=150 iu/ml. We examined the impact of changing treatment schedules over these periods. Afs cases had lower median FEV(1) %predicted (%PR) compared to matched controls 1996: 67 versus 80, P < 0.01; 2001: 78 versus 93, P < 0.01. Afs cases in the 2001 cohort had a higher FEV(1) %PR compared to Afs cases in the 1996 cohort: 78 versus 67, P < 0.01. For the 1996 Afs cohort FEV(1) %PR fell significantly over 5 years but not for the 2001 Afs cohort. Af RAST and total IgE reflected the changes in pulmonary function. Children in the 2001 Afs cohort were prescribed significantly more oral antifungal treatment (odds ratio 4.3, 95%CI 1.2-15.7, P = 0.03). Afs children continue to have poorer lung function compared to controls but this observational, hypothesis generating study, suggests that the use of antifungal treatment is associated with better lung function.     

Increased airways responsiveness in swine farmers

A respiratory questionnaire, pulmonary function tests, and an examination of airways responsiveness were conducted on 20 swine farmers and 20 control subjects. The swine farmers represented almost the complete work force from 13 Hutterite colonies and had worked in confinement buildings with more than 2,000 swine (3,270 +/- 1,221 swine) for at least four hours (6.6 +/- 1.8 hours) per day for more than two years (10.5 +/- 7.5 years). The control subjects were randomly selected from outdoor city workers from the city of Saskatoon and were matched for gender, age (+/- 2 years), and smoking status. Eleven swine farmers (55 percent) had chronic cough, compared with three (15 percent) of the control subjects (p less than 0.01). Eight (40 percent) of the swine farmers had symptoms of wheezing, compared with three (15 percent) of the control subjects (p less than 0.05). The FEV1 was significantly lower in swine farmers (97.2 +/- 11.5 percent predicted) than in control subjects (106.0 +/- 12.0 percent of predicted) (p less than 0.05). Airways responsiveness was measured by methacholine challenge with doubling concentrations ranging from 0.25 to 256 mg/ml. The provocation concentrations resulting in a reduction of 10 percent (PC10) and 20 percent (PC20) in FEV1 were lower in swine farmers than in control subjects (PC10, 77.2 +/- 78.8 mg/ml vs 180.8 +/- 96.5 mg/ml; p less than 0.01; and PC20, 154.5 +/- 99.9 mg/ml vs 229.6 +/- 66.8 mg/ml; p less than 0.05). Twelve swine farmers (60 percent) had PC20 of less than 256 mg/ml, compared with three (15 percent) of the control workers (p less than 0.01). Fewer swine farmers demonstrated atopy as measured by skin prick tests than did control workers (21 percent vs 56 percent; p less than 0.05). These findings suggested that occupational exposure in swine confinement buildings is associated with mild increases of nonspecific, nonatopic airways responsiveness in swine farmers.     

Long-term observational, non-randomized study of enzyme replacement therapy in late-onset glycogenosis type II

Objectives

Type II glycogenosis (GSDII) is a lysosomal storage disorder due to acid alpha-glucosidase (GAA) deficiency. Enzyme replacement therapy (ERT) with human recombinant alpha-glucosidase (rhGAA) has been demonstrated to be effective in the treatment of infantile forms of GSDII, but little information is available concerning late-onset phenotypes. Long-term follow-up studies are not available at present. The aim of this study was to evaluate the ERT long-term effects in late-onset GSDII.

Methods

Twenty-four patients, including 7 juveniles and 17 adults, received bi-weekly infusion of rhGAA (20 mg/kg) for at least 36 months. Clinical conditions, muscular function (6-min walking test, 6MWT; Walton scale, WS), respiratory function (vital capacity, VC; forced expiratory volume, FEV1; arterial pCO₂), and muscle enzymes were assessed every 6 months.

Results

The 6MWT improved in both juvenile and adult patients (p?=?0.01, p?=?0.0002, respectively), as well as in patients with moderate to severe muscle function impairment (WS?>?3.5; p?=?0.002). An overall improvement in WS was also observed (p?=?0.0003). VC and FEV1 remained unchanged, while pCO₂ decreased (p?=?0.017). Muscle enzymes decreased significantly (p?<?0.0001). Two patients (8%) showed transient secondary events during ERT.

Conclusions

Long-term ERT with rhGAA was shown to be safe, well tolerated, and effective in improving motor function and in stabilizing respiratory function in late-onset GSDII. The response pattern showed a progressive clinical improvement during the follow-up period in juvenile patients, while in adults it reached and maintained a plateau after the first year of treatment.     

Dust is in the Air. Part II: Effects of Occupational Exposure to Welding Fumes on Lung Function in a 9-Year Study

Purpose

Adverse health effects of work-related contact with respirable hazardous substances are of great public interest. Because related prospective and long-term follow-up studies are rare, the extent of acute and chronic pulmonary health risks of occupational exposure to welding fumes is discussed controversially in the scientific literature. The objective of the present longitudinal study during a 9-year period was to investigate the annual changes of lung function in welders.

Methods

Anthropometric measures and smoking behaviour, and spirometric tests (FVC, FEV1, and MEF50) obtained during routine occupational health checkups of female and male workers (n = 1,982) in Austria during the years 2002–2010 were analyzed.

Results

The study participants displayed average lung function values lower than the age- and sex-specific norm. Decrease in respiratory capacity was dependent on smoking habits and duration of occupational exposure. Specifically for welders (n = 1,326), decrease of pulmonary function was significantly associated with heavy smoking (FVC ?70.7 ml, p = 0.07; FEV1 ?167.4 ml, p < 0.001; MEF50 ?356.2 ml/s, p < 0.001), but not with moderate smoking habits, and also with duration of occupational exposure to welding fumes per year (FVC ?0.89 ml, p = 0.36; FEV1 ?2.91 ml, p < 0.001; MEF50 ?4.7 ml/s, p = 0.047).

Conclusions

Individual smoking habits as well as duration of occupational exposure to welding fumes showed a negative impact on lung function parameters. To reduce the risk of work-associated respiratory morbidity, smoking cessation is highly recommended to personnel engaged in welding fumes- and dust-exposed occupations.     

Long-term reproducibility of tests of small airways function. Comparisons with spirometry

We used a tracking index to measure the reproducibility of single breath nitrogen test variables (CV/VC, CC/TLC, delta N2/L) and spirometric variables (FEV1 and FEV1/FVC) and to compare the characteristics of individuals whose pulmonary function tracks well with those whose pulmonary function tracks poorly. Data were derived from two cohorts followed longitudinally over a 9-11 year period. All variables were adjusted for age, sex and height by expressing them as Z-scores. In all smoking groups and in both cohorts, the tracking index was highest for FEV1, indicating that this variable was the most reproducible over the period of follow-up; delta N2/L and FEV1/FVC had very similar but slightly lower tracking indices; CV/VC consistently had the lowest tracking indices. Tracking indices were generally higher in smokers than in nonsmokers. The reproducibility of CC/TLC increased over the period of follow-up whereas the FEV1 reproducibility remained constant. We found no significant difference between those with high tracking indices and those with low indices in terms of sex, smoking status, prevalence of respiratory symptoms, history of respiratory disease, and rate of decline of FEV1. We conclude that FEV1 is the most reproducible of the variables examined, both within and between individuals, and that poor tracking or reproducibility are not related to smoking or to the presence of respiratory symptoms or disease.     

Elevation of total serum immunoglobulin E is associated with asthma in nonallergic individuals.

Elevated serum immunoglobulin (Ig)E is the hallmark of atopy, and contributes to asthma and bronchial hyperresponsiveness in atopic individuals. In contrast, the significance of IgE in nonallergic subjects is less clear. The aim of the present study is to clarify a potential association of IgE and asthma in absence of clinical allergy. To this purpose 1,219 consecutive patients of a pulmonary practice were evaluated. Nonallergic patients were defined by negative skin prick test, history of atopy and specific IgE, 509 subjects (42%) were nonallergic. Among these, 80 patients (16%) had elevated total IgE levels (>150 U x mL(-1)). Prevalence and severity of asthma in nonallergic subjects with IgE>150 U x mL(-1) were compared with subjects with normal IgE levels, and lung function parameters were correlated with serum IgE in all nonallergic subjects and asthmatics. Asthma was more prevalent in nonallergic subjects with elevated IgE levels than in nonallergic subjects with normal IgE (39% versus 14%; p<0.001). Lung function values of nonallergic asthmatics were lower for forced expiratory volume in one second (FEV1)% predicted (66+20% versus 83+/-17%; p<0.001), FEV1% forced vital capacity (FVC) (70+/-14% versus 81+/-8%; p<0.001) and forced mid expiratory flow (FEF25-75) (1.7+/-0.9 L x s(-1) versus 2.8+/-0.9 L x s(-1); p=0.002) in patients with high IgE compared to asthmatics with normal IgE, and were negatively correlated with log IgE levels in all nonallergic asthmatics. (FEVI % pred: r=-0.5, p<0.001; FEV1% FVC: r=-0.53, p<0.001; FEF25-75: r=-0.52, p<0.001). In the whole study population, multivariate analysis showed a greater than fivefold asthma risk for nonallergic individuals with serum IgE>150 U x mL(-1). These data support the role of IgE as risk factor for asthma independent of allergy, and they further challenge the definition of intrinsic asthma as "non-IgE mediated" entity.     

Risk factors for airway remodeling in asthma manifested by a low postbronchodilator FEV1/vital capacity ratio: a longitudinal population study from childhood to adulthood

Airway remodeling may lead to irreversible loss of lung function in asthma. The impact of childhood asthma, airway responsiveness, atopy, and smoking on airway remodeling was investigated in a birth cohort studied longitudinally to age 26. A low postbronchodilator ratio of forced exhaled volume in 1 second (FEV1) to vital capacity (VC) at age 18 or 26 was used as a marker of airway remodeling. "Normal" study members with no history of asthma ever, no wheezing in the last year, and no smoking ever were used to determine sex- and age-specific reference values for this ratio. The lower limit of normal was defined as the mean ratio minus 1.96 standard deviation, delimiting the 2.5% of the normal population with the lowest FEV1/VC ratio. A low postbronchodilator FEV1/VC ratio was found in 7.4% and 6.4% of study members at ages 18 and age 26 and 4.6% at both assessments. Lung function was low throughout childhood in those with a consistently low postbronchodilator FEV1/VC ratio at both ages. Those with consistently low postbronchodilator ratios also showed a greater decline in the prebronchodilator FEV1/VC ratio from ages 9 to 26 compared with those with normal postbronchodilator ratios at both ages (males, -12% versus -6%, p < 0.0001; females, -10.5% versus -5.5%, p < 0.01). Asthma, male sex, airway hyperresponsiveness, and low lung function in childhood were each independently associated with a low postbronchodilator FEV1/VC ratio, which in turn was associated with an accelerated decline in lung function and decreased reversibility. These data suggest that airway remodeling in asthma, as manifested by impaired lung function, begins in childhood and continues into adult life.     

The effects of airway hyperresponsiveness, wheezing, and atopy on longitudinal pulmonary function in children: a 6-year follow-up study.

We examined growth of spirometric lung function in 696 children of European ancestry who were followed from ages 9 to 15 years and stratified according to their degree of responsiveness to methacholine inhalation challenge, atopic status, and respiratory symptoms. Subjects were participants in the longitudinal Multidisciplinary Health and Development Study in Dunedin, New Zealand. Forced expired volume in 1 second (FEV1), and vital capacity (VC) were measured at 9, 11, 13, and 15 years of age, concurrently with assessment of airway responsiveness determined by the concentration of methacholine causing a 20% fall in FEV1 (PC20 FEV1). Atopic status was assessed at age 13 by skin-prick testing to 11 allergens. In children demonstrating airway hyperresponsiveness, FEV1 increased with age at a slower rate, and the FEV1/VC ratio had a faster rate of decline through childhood, compared to non-responsive children. Subjects with positive skin tests to house dust mite and cat dander also had lower mean FEV1/VC ratios than the control group. Any reported wheezing was associated with slower growth of FEV1 and VC in males. We conclude that in New Zealand children with airway responsiveness and/or atopy to house dust mite or cat growth of spirometric lung function is impaired.     

Allergic bronchopulmonary aspergillosis in cystic fibrosis. A European epidemiological study. Epidemiologic Registry of Cystic Fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a disease resulting from a hypersensitivity response to Aspergillus fumigatus, although the pathogenesis of the disease is unknown and its prevalence in cystic fibrosis (CF) is still poorly defined. Data from the Epidemiologic Registry of Cystic Fibrosis (ERCF) on 12,447 CF patients gathered from 224 CF centres in nine European countries were analysed. The ERCF definition of ABPA diagnosis is a positive skin test and serum precipitins to A. fumigatus, together with serum immunoglobulin (Ig)E levels >1,000 U x mL(-1) and additional clinical or laboratory parameters. The overall prevalence of ABPA in the ERCF population was 7.8% (range: 2.1% in Sweden to 13.6% in Belgium). Prevalence was low <6 yrs of age but was almost constant approximately 10% thereafter. No sex differences were observed. ABPA affected 8.0% of patients with a deltaF508/deltaF508 genotype and 5-6% with deltaF508/G551D, deltaF508/G542X and deltaF508/N1303K genotypes. ABPA patients presented a lower forced expiratory volume in one second (FEV1) than those without ABPA at any age and the prevalence ranged from 6.6% in patients with FEV1 > or =20-12.9% in those with FEV1 <40%. ABPA was associated with higher rates of microbial colonization, pneumothorax and massive haemoptysis, and with higher IgG serum levels and poorer nutritional status. A mixed model regression analysis of lung function showed that FEVI decline during the follow-up period was not substantially different in ABPA patients compared with non-ABPA patients for any subgroups based on age or disease severity at enrollment. To conclude, allergic bronchopulmonary aspergillosis is a frequent complication in cystic fibrosis patients, particularly after the age of 6 yrs, and it is generally associated with a poorer clinical condition. However, any clear independent influence of allergic bronchopulmonary aspergillosis on the rate of lung function decline in the short term was not shown.     

Correlation of IgE antibody titer to Aspergillus fumigatus with decreased lung function in cystic fibrosis

Obstructive pulmonary disease is a typical feature of cystic fibrosis (CF) and is often associated with bronchial hyperreactivity. Positive skin-test reactions to Aspergillus fumigatus antigens are frequently seen even in nonatopic patients with CF. Full-fledged allergic bronchopulmonary aspergillosis (ABPA) has been estimated to occur in 10% of patients with CF. The relationship between lung function and presence of IgE antibodies to Aspergillus antigens in patients without ABPA is not clear. In 148 outpatients with CF (aged 6-34 years) specific immunoglobulin E (IgE) to Aspergillus fumigatus antigens, basic lung-function parameters, and bronchial response to salbutamol were measured. Multiple regression was performed for age, weight as percentile for actual height (indicating general condition), and Aspergillus RAST. Aspergillus IgE was present in 46% of patients; 19% had RAST class 3 or 4. Independent negative correlations of Aspergillus RAST with FEV1, FEF50%, FEF25%, RV, Chrispin Norman score, and sRaw (P less than 0.05) were found. Bronchodilator sensitivity did not correlate significantly with age and weight percentile. However, Aspergillus RAST did correlate significantly with bronchodilator response measured by sRaw (P less than 0.05). High titers of Aspergillus RAST might serve as a selective criterion for patients to be included in future studies evaluating broncholytic or antiphlogistic therapies.