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Respiratory symptoms and lung function in alumina refinery employees.

OBJECTIVES: Employees in alumina refineries are known to be exposed to a number of potential respiratory irritants, particularly caustic mist and bauxite and alumina dusts. To examine the prevalence of work related respiratory symptoms and lung function in alumina refinery employees and relate these to their jobs. METHODS: 2964 current employees of three alumina refineries in Western Australia were invited to participate in a cross sectional study, and 89% responded. Subjects were given a questionnaire on respiratory symptoms, smoking, and occupations with additional questions on temporal relations between respiratory symptoms and work. Forced expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC) were measured with a rolling seal spirometer. Atopy was assessed with prick skin tests for common allergens. Associations between work and symptoms were assessed with Cox's regression to estimate prevalence ratios, and between work and lung function with linear regression. RESULTS: Work related wheeze, chest tightness, shortness of breath, and rhinitis were reported by 5.0%, 3.5%, 2.5%, and 9.5% of participants respectively. After adjustment for age, smoking, and atopy, most groups of production employees reported a greater prevalence of work related symptoms than did office employees. After adjustment for age, smoking, height, and atopy, subjects reporting work related wheeze, chest tightness, and shortness of breath had significantly lower mean levels of FEV(1) (186, 162, and 272 ml respectively) than subjects without these symptoms. Prevalence of most work related symptoms was higher at refinery 2 than at the other two refineries, but subjects at this refinery had an adjusted mean FEV(1) >60 ml higher than the others. Significant differences in FVC and FEV(1)/FVC ratio, but not FEV(1), were found between different process groups. CONCLUSIONS: There were significant differences in work related symptoms and lung function between process groups and refineries, but these were mostly not consistent. Undefined selection factors and underlying population differences may account for some of these findings but workplace exposures may also contribute. The differences identified between groups were unlikely to be clinically of note.

Air Pollutants, Occupational↗

Respiratory symptoms and lung function in workers in heavy and highway construction: a cross-sectional study.

BACKGROUND: Occupational exposures for workers in heavy and highway (HH) construction include cement-containing dusts and diesel exhaust (DE). To investigate possible health effects, respiratory symptoms and lung function were examined in laborers, tunnel workers (TW), and operating engineers (OE) in HH and tunnel construction. The principal outcome of interest was airways disease. METHODS: Subjects were recruited through their unions. Medical and occupational histories and flow-volume loops were obtained. Based on self-report, asthma and chronic bronchitis were categorized as (1) physician-diagnosed or (2) for asthma, undiagnosed likely, and (3) for chronic bronchitis, symptomatic. Trade and time in the union were used as surrogates of exposure. Prevalence of asthma and chronic bronchitis, lung function outcome, and relationships with exposure variables were examined. RESULTS: Data were obtained on 389 workers: 186 laborers, 45 TWs, and 158 OEs. Prevalence of asthma was 13 and 11.4% for laborers (including TW) and OEs, respectively, and of symptomatic chronic bronchitis, 6.5 and 1.9%, respectively. Odds ratios (OR) for undiagnosed asthma likely were significantly elevated in TWs compared to OEs, and marginally elevated for chronic bronchitis. Inverse relationships were observed between time in the union, and risk for asthma and chronic bronchitis. Asthma (physician-diagnosed or undiagnosed likely) predicted lower FEV(1). Current cigarette use was associated with chronic bronchitis but not asthma. CONCLUSIONS: TWs, laborers, and OEs in HH construction are at increased risk for asthma. TWs also appear to be at increased risk for chronic bronchitis. Our data suggest that symptomatic workers are self-selecting out of their trade. Asthma was associated with lower lung function in those affected.

Adult↗

The relationship between low level nitrogen dioxide exposure and child lung function after cold air challenge.

BACKGROUND: Nitrogen dioxide (NO(2)) or home gas appliance use has been inconsistently associated with adverse respiratory outcomes in childhood. OBJECTIVES: (i) To examine the contribution of home gas appliance type and personal NO(2) exposure. (ii) To examine the relationship between NO(2) exposure and child lung function and respiratory history. (iii) To assess whether these relationships vary by house dust mite sensitization status. METHODS: A cross-sectional survey of 344 children (71% of the eligible group) with a mean age of 9.1 years from four randomly selected schools in the Australian Capital Territory from July to September 1999. Study measurements included a parental questionnaire, NO(2) exposure by passive gas samplers, skin prick testing for 10 aeroallergens and lung function at rest and after cold air challenge. RESULTS: Total NO(2) exposure was low with a mean concentration of 10.1 ppb. No associations were found between NO(2) exposure or gas appliance use and asthma, wheeze or baseline lung function. Personal NO(2) exposure was associated with a reduction in forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) after cold air challenge (adjusted difference - 0.12% (- 0.23% to - 0.01%) per 1 ppb increase). After exclusion of children who had home heating changed because of asthma, gas heater use was also significantly associated with a reduction in this measure (adjusted difference - 2.0% (- 3.7% to - 0.2%)). There was some evidence that these reductions were greater among the non-mite-sensitized children. CONCLUSIONS: The effect of low-level NO(2) exposure on these respiratory outcomes was not marked. The possible effect of low-level NO(2) exposure on non-specific bronchial reactivity requires confirmation. Future studies on NO(2) and respiratory health should include measures of house dust mite sensitization and bronchial hyper-responsiveness.

Air↗

Development of fibrosis after lung irradiation in relation to inflammation and lung function in a mouse strain prone to fibrosis.

The development of lung fibrosis after single-dose thoracic irradiation was studied histologically in C57L/J male mice. Lung function was monitored using uptake of carbon monoxide. During the latent period (prior to 15 weeks postirradiation) mice were chosen at random, while during the early phase (15-22 weeks) mice were sacrificed when they developed a functional deficit of at least 50%. Excess mice with a deficit of 50% in the early phase were followed into the late phase and sacrificed at 31 or 40 weeks. Two scoring methods were used to quantify lung damage. Fibrotic lesions and foci of inflammation were counted for the latent period, and the proportion of nonfunctional acini was determined for the early and late phases. After a dose 1 Gy less than the LD50/180, small regions of mild inflammatory infiltration appeared at 6 weeks, and small, focal fibrotic lesions containing numerous macrophages appeared at 8 weeks postirradiation. The number of fibrotic lesions increased steadily during the latent period in a manner that is consistent with conversion of inflammatory lesions to foci of fibrosis. Mice sacrificed upon developing a 50% functional deficit during the early phase had approximately equal proportions of lung affected by fibrosis and inflammation. Those mice which developed a similar respiratory deficit in the early phase and were followed into the late phase usually showed little change in lung function. However, when sacrificed at 31 weeks they had twice as much fibrosis and very little inflammation, suggesting that the inflammatory lesions had become fibrosed. The average number of macrophages per unit area of fibrosis declined during the latent period and changed little during the early and late phases. Lymphocytes and mast cells were also quantified in fibrosed regions.

Animals↗

Physical and biological predictors of changes in whole-lung function following thoracic irradiation.

PURPOSE: To develop methods of predicting the pulmonary consequences of thoracic irradiation (RT) by prospectively studying changes in pulmonary function following RT. METHODS AND MATERIALS: 100 patients receiving incidental partial-lung irradiation during treatment of tumors in or adjacent to the thorax had whole-lung function assessed via symptoms and pulmonary function tests (PFTs: FEV1-forced expiratory volume 1 s; DLCO-diffusion capacity) before and repeatedly 6-48 months following RT. All had computed tomography-based three-dimensional (3D) dose calculations with lung density heterogeneity corrections for dose-volume histogram (DVH) and normal tissue complication probability (NTCP) calculations. Functional DVHs (DVfH) based on SPECT (single photon emission computed tomography) lung perfusion scans, and serial transforming growth factor-beta (TGF-beta1) levels were available in 50 and 48 patients, respectively. The incidence and severity of changes in whole-lung function were correlated with clinical, physical, and biological factors. Exploratory statistical analyses were performed using chi-square, Pearson correlations, logistic regression, and multiple linear regression. RESULTS: RT-induced symptoms developed in 21 patients. In the overall group, the single best predictor for the development of symptoms was the NTCP (p < 0.05). Pre-RT PFTs alone were less predictive (p = 0.1 for FEV1, p = 0.08 for DLCO). A multivariate model based on pre-RT DLCO and CT-based NTCP was strongly predictive for the development of symptoms (p < 0.001). NTCPs based on SPECT-derived DVf Hs and TGF-beta1 levels did not appear to provide additional predictive value. The presence or absence of pulmonary symptoms was correlated with the decline in PFT 6 months following RT (p < 0.05). In the overall group, the degree of decline in PFTs was not well correlated with any of the dose-volume variables considered. In patients with "good" pre-RT PFTs, there was a relationship between the percent reduction in PFT and dose-volume parameters such as the percent of lung volume receiving > 30 Gy (p < 0.05). CONCLUSION: The extent of alteration in whole-lung function (symptoms or PFT changes) appears to be related to both dose-volume and pre-RT PFT parameters. The data suggest that no one variable is likely to be an adequate predictor and that multivariate predictive models will be needed. Additional studies are underway to develop better predictive models that consider physical factors such as the DVH and regional perfusion, as well as biological/clinical factors such as pre-RT PFTs and TGF-beta1.

Adult↗

Association of lung function decline with the heme oxygenase-1 gene promoter microsatellite polymorphism in a general population sample. Results from the European Community Respiratory Health Survey (ECRHS), France.

Inducible heme oxygenase (HO-1) acts against oxidants that are thought to play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD), characterised by impaired lung function. A (GT)(n) repeat polymorphism in the HO-1 gene promoter can modulate the gene transcription in response to oxidative stress. We hypothesised that this polymorphism could be associated with the level of lung function and decline in subjects exposed to oxidative aggression (smokers). We genotyped 749 French subjects (20-44 years, 50% men, 40% never smokers) examined in both 1992 and 2000 as part of the ECRHS. Lung function was assessed by forced expiratory volume in 1 second (FEV1) and FEV1/forced ventilatory capacity (FVC) ratio. We compared long (L) allele carriers ((GT)(n) > or =33 repeats for one or two alleles) to non-carriers. Cross sectionally, in 2000, L allele carriers showed lower FEV1/FVC than non-carriers. During the 8 year period, the mean annual FEV1 and FEV1/FVC declines were -30.9 (31.1) ml/year and -1.8 (6.1) U/year, respectively. FEV1/FVC decline was steeper in L allele carriers than in non-carriers (-2.6 (5.5) v -1.5 (6.4), p = 0.07). There was a strong interaction between the L allele and smoking. In 2000, the L allele was associated with lower FEV(1) and FEV(1)/FVC in heavy smokers (> or =20 cigarettes/day) only (p for interaction = 0.07 and 0.002 respectively). Baseline heavy smokers carrying the L allele showed the steepest FEV1 decline (-62.0 (29.5 ml/year) and the steepest FEV1/FVC decline (-8.8 (5.4 U/year) (p for interaction = 0.009 and 0.0006). These results suggest that a long (L) HO-1 gene promoter in heavy smokers is associated with susceptibility to develop airway obstruction.

Adult↗

Reduced lung function in healthy preterm infants in the first months of life.

RATIONALE: Preterm delivery has been associated with a higher incidence of respiratory morbidity even in infants that do not have significant respiratory disease during the neonatal period. Reduced flows have been reported in children and adolescents born prematurely. OBJECTIVE: The aim of this study was to assess lung function in healthy preterm infants in the first months of life. METHODS: Preterm infants with less than 48 h of supplemental oxygen were recruited. Lung function was assessed by the raised-volume rapid thoracic compression in the first months of life. The control group consisted of full-term infants without a history of respiratory diseases. MEASUREMENTS AND MAIN RESULTS: Sixty-two preterm (29 male) and 27 full-term (10 male) infants were tested. Adjusting for length, age, and sex, we found a mean significant reduction of 92 ml/s (22%) in FEF(50), 73 ml/s (21%) in FEF(25-75), and 19 ml (28%) in FEV(0.5) in the preterm group. These differences in expiratory flows remained significant using another model that adjusts for lung volume (p < 0.01 for FEF(50), FEF(25-75), and FEV(0.5), and p < 0.05 for FEF(75)). In the preterm group, after adjusting for length, male sex, lower gestational age, and increased weight were significantly and independently associated with reduced flows. CONCLUSIONS: Our findings confirm that prematurity is independently associated with reduced lung function and that this is detectable in the first months of life. Male sex, lower gestational age, and weight are important predictors for reduced expiratory flows in this group.

Child, Preschool↗

Lung function and methacholine responsiveness among adolescents in an air-polluted area.

BACKGROUND: Outdoor air pollution is hazardous to human pulmonary health. Airway inflammation is an important cause of bronchial hyperresponsiveness. Information is not univocal about the potential effects of prolonged exposure to environmental air pollutants on lung function. OBJECTIVES: A cross-sectional study was performed to assess bronchial responsiveness to methacholine in children living in an air-polluted area. Afterwards, the same study protocol was repeated in children of similar age living in mountain valleys with virtually no air pollution. METHODS: Every child underwent a lung function test, skin tests to common allergens, total serum levels of IgE, and a challenge to methacholine at increasing doses (PD20 FEV1). Subjects were 246 children 11-12 years old living in an air-polluted area, and 285 children 11-13 years old living in mountain valleys. Respectively, 156 and 161 were negative to skin tests and had serum total IgE<100 IU/ml, and had no asthma or other recurrent or ongoing respiratory symptoms. RESULTS: Lung function data, adjusted for the effect of potential confounders showed significantly lower FVC, and even more so FEV1, in the children from the polluted area. After the exclusion of subjects with positive skin tests and serum total IgE>100 IU/ml and those with history of asthma or respiratory disorders, there were higher percentages of positive responses in the challenge to methacholine in children from the polluted area (28.9 vs. 15.5%, p<0.001). CONCLUSIONS: These data may corroborate the possible importance of long exposure to air pollutants on the prevalence of bronchial aspecific hyperresponsiveness in otherwise normal children.

Adolescent↗

Maximal expiratory flows at functional residual capacity: a test of lung function for young children.

Maximal expiratory flows at functional residual capacity were measured noninvasively from partial expiratory flow-volume curves in 65 awake, healthy children, 4 to 6 years of age. The variabilities within and between subjects were nearly identical to those reported for flows low in the vital capacity obtained from older subjects. This test of maximal expiratory flow at functional residual capacity has the advantage that the subject does not have to inspire to total lung capacity, exhale to residual volume, or make a maximal effort, and it is therefore applicable to the testing of young children who cannot perform a vital capacity maneuver. Measurement of this flow rate in 20 patients of the same age with lung disorders of varying severity revealed abnormal flow rates in more than 50 per cent of patients. Functional residual capacity was measured by the closed-circuit helium-equilibration method. When flow rates in liters per sec were compensated for lung size, girls had significantly larger flow rates than did boys. This suggests that the lungs of young children may grow differently according to genetic determinants related to sex.

Adolescent↗

The intensive care unit oxygen challenge should not be used for donor lung function decision-making.

BACKGROUND: The intensive care unit oxygen challenge is a routine screening test for donor lung function. An arterial PO2 of <300 mm Hg is generally considered evidence of inadequate pulmonary function that contraindicates the use of the lungs for transplantation. METHODS: Between December 1, 2001 and January 24, 2004, the intensive care unit oxygen challenge was compared with the PO2 in samples drawn from each pulmonary vein confluence in the operating room in 91 donors (182 donor lungs) after the lungs were fully inflated (FIO2 1.0). There were 62 males and 29 females, with a median age of 27.5 years (13.6 to 55.4 years). RESULTS: In 40 lungs, the pulmonary vein PO2 was >300 mm Hg, whereas the PO2 was <300 mm Hg on the last intensive care unit O2 challenge. The difference between the intensive care unit PO2 and the operating room pulmonary vein PO2 was greatest for donors with the lowest intensive care unit PO2. Of these 40 lungs, 8 were transplanted, all of whom had excellent graft function with a median intubation of 14.2 hours (6.1 to 23.8 hours). No patient sustained primary graft failure or an airway complication. CONCLUSIONS: The intensive care unit PO2 is an unreliable screening test for donor lung function, particularly when one lung is clear and the other is unclear radiographically. In this setting, intraoperative surgical assessment and pulmonary venous PO2 should be the basis for determining donor lung suitability. This strategy may provide an opportunity to increase donor lung availability.

Adolescent↗

X-ray findings, lung function, and respiratory symptoms in black South African vermiculite workers.

Health effects have been documented among American vermiculite workers who mined and processed vermiculite contaminated with amphibole asbestos, viz., tremolite-actinolite. Workers mining and processing South Africa vermiculite (N = 172), which contains very little asbestos, underwent x-ray examination and lung function testing and completed a respiratory symptom questionnaire. The vermiculite workers were compared with other workers involved in the mining or refining of copper. Only two of the vermiculite workers showed evidence of small opacities of 1/0 or more (according to the ILO 1980 classification); lung function was comparable with the other groups of workers, and there was no excess of respiratory symptoms among the vermiculite workers. It is concluded that workers exposed to vermiculite that is minimally contaminated with asbestos are probably not at risk for pneumoconiosis, lung function impairment, or respiratory symptoms. It is likely that the health effects observed in other studies of vermiculite workers are the result of concomitant asbestos exposure. A risk of mesothelioma caused by the fiber content of the vermiculite cannot be excluded by this study.

Adult↗

Decline in lung function in lymphangioleiomyomatosis: relation to menopause and progesterone treatment.

The progression of lymphangioleiomyomatosis, a rare lung disease in women, is thought to be influenced by hormonal factors. We studied the rate of decline in FEV(1) and carbon monoxide transfer factor (TL(CO)) in a national cohort of patients with lymphangioleiomyomatosis in the United Kingdom and its relation to two factors that might influence the disease, menopausal status and progesterone treatment. We used retrospective data from hospital notes, and of the 50 patients identified 43 had suitable lung function data spanning at least 3 mo. Mean (SD) annual decline in FEV(1) was 118 (142) ml for all patients, and these figures changed little when only data spanning at least 2 and 3 yr were analyzed. There was considerable variation in the rate of decline between subjects, however, and although it tended to be less among postmenopausal women and those receiving progesterone, patient numbers were smaller and the findings were not significant. There was a significant reduction in decline in TL(CO) in premenopausal patients receiving progesterone and in both FEV(1) and TL(CO) after starting progesterone in six patients who had data before and after starting treatment. This study documents the rapid decline in lung function in lymphangioleiomyomatosis, confirms the wide variation between patients, and provides some support for the suggestion that disease progression may be reduced by progesterone. The data provide a basis for designing prospective studies of treatment for lymphangioleiomyomatosis.

Adult↗

Lung function and within-breath changes in resistance in patients who have had a laryngectomy.

We describe the construction of a simple device which may be used to connect a patient with a tracheostomy to standard lung function testing equipment. We compared the lung function of nine patients after laryngectomy with nine patients matched for similar degrees of airflow obstruction, and found that peak flow rate (as per cent predicted) was significantly lower than predicted FEV1 in the patients with tracheostomy. This suggests that the larynx may normally affect production of peak flow. We then compared the change in resistance over the normal tidal volume in the two groups, finding no significant difference, and obtained similar results from paired studies in two patients before and after laryngectomy. We conclude that, while the laryngeal aperture varies during tidal breathing, it plays no major part in the overall resistance changes which occur during a normal breath.

Adult↗

Decline in lung function in patients with lymphangioleiomyomatosis treated with or without progesterone.

STUDY OBJECTIVE: Lymphangioleiomyomatosis (LAM), a disease affecting women and causing cystic lung lesions, and, in some instances, leading to respiratory failure and death, appears to be exacerbated by estrogens. Hence, hormonal therapy with progesterone is frequently employed; however, efficacy has not been demonstrated. Our aim was to determine whether progesterone administration slowed the decline in lung function in LAM. DESIGN: Retrospective study. SETTING: National Institutes of Health, Bethesda, MD. DESIGN AND SUBJECTS: The study population comprised 348 patients with LAM participating in a longitudinal research protocol. Declines in diffusion capacity of the lung for carbon monoxide (Dlco) and FEV(1) were measured in 275 patients observed for approximately 4 years. The declines in Dlco and FEV(1) of patients treated with progesterone, po (n = 67) or IM (n = 72), were compared with those of untreated patients (n = 136). MEASUREMENTS AND RESULTS: Overall yearly rates of decline in Dlco and FEV(1) were 2.4 +/- 0.4% predicted (0.69 +/- 0.07 mL/min/mm Hg) and 1.7 +/- 0.4% predicted (75 +/- 9 mL), respectively (mean +/- SEM). The most significant predictors of functional decline were initial lung function and age. After adjusting for initial FEV(1), age, and duration of disease, patients treated with IM progesterone tended to have lower rates of decline in FEV(1) than patients treated po (1.9 +/- 0.6% predicted vs 3.2 +/- 0.8% predicted, respectively; p = 0.081). However, there was no significant difference in rates of decline in FEV(1) between patients treated with IM progesterone and untreated patients (1.9 +/- 0.6% predicted vs 0.8 +/- 0.5% predicted, respectively; p = 0.520), and patients treated with po progesterone and untreated patients (3.2 +/- 0.8% predicted vs 0.8 +/- 0.5% predicted, respectively; p = 0.064). After adjusting for initial Dlco, rates of decline in Dlco were significantly higher in patients treated with po progesterone (3.6 +/- 0.7% predicted, p = 0.002) and IM progesterone (2.8 +/- 0.5% predicted, p = 0.022) than in untreated patients (1.6 +/- 0.6% predicted). CONCLUSIONS: Within the limitations of a retrospective study, our data suggest that progesterone therapy does not slow the decline in lung function in LAM.

Adult↗

Dietary magnesium, lung function, wheezing, and airway hyperreactivity in a random adult population sample.

Magnesium is involved in a wide range of biological activities, including some that may protect against the development of asthma and chronic airflow obstruction. We tested the hypothesis that high dietary magnesium intake is associated with better lung function, and a reduced risk of airway hyper-reactivity and wheezing in a random sample of adults. In 2633 adults aged 18-70 sampled from the electoral register of an administrative area of Nottingham, UK, we measured dietary magnesium intake by semiquantitative food-frequency questionnaire, lung function as the 1-sec forced expiratory volume (FEV1), and atopy as the mean skin-prick test response to three common environmental allergens. We measured airway reactivity to methacholine in 2415 individuals, defining hyper-reactivity as a 20% fall in FEV1 after a cumulative dose of 12.25 mumol or less. Mean (SD) daily intake of magnesium was 380 (114) mg/day. After adjusting for age, sex, and height, and for the effects of atopy and smoking, a 100 mg/day higher magnesium intake was associated with a 27.7 (95% CI, 11.9-43.5) mL higher FEV1, and a reduction in the relative odds of hyper-reactivity by a ratio of 0.82 (0.72-0.93). The same incremental difference in magnesium intake was also associated with a reduction in the odds of self-reported wheeze within the past 12 months, adjusted for age, sex, smoking, atopy, and kilojoule intake, by a ratio of 0.85 (0.76-0.95). Dietary magnesium intake is independently related to lung function and the occurrence of airway hyper-reactivity and self-reported wheezing in the general population. Low magnesium intake may therefore be involved in the aetiology of asthma and chronic obstructive airways disease.

Adult↗

Gender differences in the impact of adolescent smoking on lung function and respiratory symptoms. the Nord-Trøndelag Health Study, Norway, 1995-1997.

Girls take up smoking at least as frequently as boys. Few studies have focused on gender differences in the impact of adolescent smoking. We evaluated the sex-specific effect of adolescent smoking on respiratory symptoms and lung function. All students in junior high and high schools in Nord-Trøndelag County Norway, 1995-97, were invited to participate in a cross-sectional study. Information on smoking habits and respiratory symptoms was obtained by self-administered questionnaires. Spirometry was performed in accordance with ATS standards. Eight-thousand-three-hundred and five students (83%) completed both questionnaire and spirometry. Among 6811 students aged 13-18 years (50.3% girls) with no history of asthma, 2993 (43.9%) reported never smoking, 665 (98%) reported occasional smoking, and 667 (9.9%) reported daily smoking (mean initiation age: 13.9 years). More boys than girls were heavy smokers. In all smoking categories, smokers reported a higher prevalence of respiratory symptoms than nonsmokers; symptoms increased with smoke burden. Girls reported more symptoms compared to boys with comparable smoke burden. A dose-response relation between smoking and reduced lung function was found only in girls. Girls were more vulnerable than boys to the impact of smoking on respiratory symptoms and lung function.

Adolescent↗

The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function.

The matrix metalloproteinases (MMPs) comprise a family of at least 20 proteolytic enzymes that play an essential role in tissue remodeling. MMP1 (interstitial collagenase), MMP9 (gelatinase B) and MMP12 (macrophage elastase) are thought to be important in the development of emphysema. A number of naturally occurring polymorphisms of human MMP gene promoters have been identified and found to alter transcriptional activity. Additionally, we detected a novel polymorphism in the MMP12 coding region (Asn357Ser). The aim of this study was to investigate the role of MMP polymorphisms in the development of chronic obstructive lung disease. We determined the prevalence of these polymorphisms in 590 continuing smokers chosen from the National Heart Lung and Blood Institute, Lung Health Study for having the fastest (n = 284) and slowest (n = 306) 5 year rate of decline of lung function. Of the five polymorphisms, only G-1607GG was associated with a rate of decline in lung function. The -1607GG allele was associated with a fast rate of decline (P = 0.02) [corrected]. However, haplotypes consisting of alleles from the MMP1 G-1607GG and MMP12 Asn357Ser polymorphisms were associated with rate of decline of lung function (P = 0.0007). These data suggest that polymorphisms in the MMP1 and MMP12 genes, but not MMP9, are either causative factors in smoking-related lung injury or are in linkage disequilibrium with causative polymorphisms.

Base Sequence↗

Classifying asthma severity in children: mismatch between symptoms, medication use, and lung function.

Current guidelines for asthma care categorize asthma severity based on the frequency of asthma symptoms, medication use, and lung function measures. The objective of this study was to determine whether lung function measures are consistent with levels of asthma severity as defined by the National Asthma Education and Prevention Program/Expert Panel Report 2 Guidelines. Parents of children aged 5-18 years with asthma seen in two outpatient subspecialty clinics completed questionnaires regarding asthma medication use and symptom frequency over the preceding 1 and 4 weeks, respectively. All children performed spirometry. When asthma severity was based on the higher severity of asthma symptom frequency or medication use, asthma was mild intermittent in 6.9% of participants, mild persistent in 27.9%, moderate persistent in 22.4%, and severe persistent in 42.9%. FEV(1) % predicted did not differ by level of asthma severity. FEV(1)/FVC decreased as asthma severity increased (p < 0.0001) and was abnormal in 33% of the participants, and a greater percentage of participants had an abnormal FEV(1)/FVC as asthma severity increased (p = 0.0001). In children, asthma severity classified by symptom frequency and medication usage does not correlate with FEV(1) categories defined by National Asthma Education and Prevention Program Guidelines. FEV(1) is generally normal, even in severe persistent childhood asthma, whereas FEV(1)/FVC declines as asthma severity increases.

Adolescent↗