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Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder that occurs in 10% to 15% of people who smoke, an estimated 16 million Americans. Asthma is also common. Spirometry is generally used to detect early COPD in smokers and to evaluate patients with respiratory symptoms. Although COPD and asthma account for most obstructive lung diseases, a broad spectrum of other disorders, including bronchiectasis, upper airway lesions, bronchiolar diseases, and some interstitial lung diseases, are associated with airflow obstruction. These less common forms of obstructive lung diseases are often misdiagnosed because of their uncommon occurrence and poor recognition. We describe the heterogeneous spectrum of disorders that can present with evidence of airflow obstruction and outline a diagnostic approach to obstructive lung disease.

Objective: We and others have observed significant hyperinflation and airflow obstruction after the surgical repair of pulmonary atresia and ventricular septal defect. This study sought to objectively characterize this problem and determine the prevalence of airway hyperresponsiveness in these patients. Methods: We performed a prospective study of children and young adults with pulmonary atresia and ventricular septal defect between June 1996 and December 1998. The participants were stratified into 2 distinct molecular genotypes on the basis of chromosome 22q11.2 microdeletion. A clinical diagnosis of asthma and an objective assessment of airway hyperresponsiveness were determined by means of an asthma inventory scale and methacholine challenge testing, respectively. Thirty-three patients were enrolled. Thirteen had velocardiofacial syndrome, each with chromosome 22q11.2 microdeletion. Results: None of the nonsyndromic patients had evidence for haploinsufficiency. Overall, 66.7% (22/33) met criteria for a clinical diagnosis of airway hyperresponsiveness: 62% (8/13) from the microdeletion genotype and 70% (14/20) from the nonsyndromic group. Conclusions: We have identified an extremely strong association between pulmonary atresia and ventricular septal defect and persistent airway hyperresponsiveness. Haploinsufficiency at chromosome 22q11.2 did not contribute to this predilection for airway hyperresponsiveness. These results provide a basis to anticipate persistent respiratory difficulties after operations in patients with pulmonary atresia and ventricular septal defect. Moreover, this at-risk patient population may yield unique insights into fundamental mechanisms involved in the pathogenesis of airway hyperresponsiveness. J Thorac Cardiovasc Surg 2001;122:169-77

To evaluate methods used to document changes in airway function during and after exercise, we studied nine subjects with exercise-induced asthma and five subjects without asthma. Airway function was assessed from measurements of pulmonary resistance (Rl) and forced expiratory vital capacity maneuvers. In the asthmatic subjects, forced expiratory volume in 1 s (FEV1) fell 24 ± 14% and Rl increased 176 ± 153% after exercise, whereas normal subjects experienced no change in airway function (Rl−3 ± 8% and FEV1−4 ± 5%). During exercise, there was a tendency for FEV1 to increase in the asthmatic subjects but not in the normal subjects. Rl, however, showed a slight increase during exercise in both groups. Changes in lung volumes encountered during exercise were small and had no consistent effect on Rl. The small increases in Rl during exercise could be explained by the nonlinearity of the pressure-flow relationship and the increased tidal breathing flows associated with exercise. In the asthmatic subjects, a deep inspiration (DI) caused a small, significant, transient decrease in Rl 15 min after exercise. There was no change in Rl in response to DI during exercise in either asthmatic or nonasthmatic subjects. When percent changes in Rl and FEV1 during and after exercise were compared, there was close agreement between the two measurements of change in airway function. In the groups of normal and mildly asthmatic subjects, we conclude that changes in lung volume and DIs had no influence on Rl during exercise. Increases in tidal breathing flows had only minor influence on measurements of Rl during exercise. Furthermore, changes in Rl and in FEV1 produce equivalent indexes of the variations in airway function during and after exercise.

To investigate the association of chronic obstructive pulmonary disease (COPD) with mild cognitive impairment (MCI) and MCI subtype: amnestic MCI and nonamnestic MCI, in a population-based study of elderly patients.Participants included 1927 individuals aged 70 to 89 years enrolled in the population-based Mayo Clinic Study of Aging. Participants were evaluated by using a nurse assessment, neurological evaluation, and neuropsychological testing, and the diagnosis of MCI was made by a consensus panel according to the standardized criteria. Chronic obstructive pulmonary disease was identified by the review of medical records. The study was conducted from October 1, 2004, through July 31, 2007. The associations of COPD and disease duration with MCI and its subtypes were evaluated by using logistic regression models adjusted for potential covariates.Of 1927 participants, 288 had COPD (men vs women: 18% vs 12%; P.001). As compared with patients without COPD, patients with COPD had a higher prevalence of MCI (27% vs 15%; P.001). The odds ratio (OR) for MCI was almost 2 times higher in patients with COPD than in those without (OR, 1.87; 95% CI, 1.34-2.61), with a similar effect in men and women. The OR for MCI increased from 1.60 (95% CI, 0.97-2.57) in patients with a COPD duration of 5 years or less to 2.10 (95% CI, 1.38-3.14) in patients with a COPD duration of more than 5 years.This population-based study suggests that COPD is associated with increased odds of having MCI and its subtypes. There was a dose-response relationship with the duration of COPD after controlling for the potential covariates.

To the Editor: We recently found that azithromycin taken daily for 1 year reduced the frequency of acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) in subjects who were selected as having an increased risk of exacerbations [1]. Since azithromycin has potentially adverse effects, identifying patients most likely to benefit might be useful for targeting therapy. Accordingly, we included a substudy in our trial that was prospectively designed to determine whether plasma levels at entry, or a change in levels at 3 months of any of four blood biomarkers, were associated with improved clinical response to azithromycin as compared to placebo. We chose to study biomarkers of inflammatory pathways likely to be relevant to chronic obstructive pulmonary disease (COPD) including C-reactive protein (CRP), interleukin (IL)-6, IL-8 and soluble tumour necrosis factor receptor 75 (sTNFR75). The parent trial comprised 1142 subjects with COPD randomised to receive azithromycin (250 mg orally each day) or placebo (1:1) for 12 months (ClinicalTrials.gov NCT00325897) [1]. To enrich our population for subjects more likely to have an AECOPDs, we required that subjects used either systemic corticosteroids, visited an emergency room or were hospitalised for AECOPD in the preceding 12 months or were using continuous supplemental oxygen [2]. We required subjects to be free of AECOPDs or other acute illness for ≥4 weeks prior to enrolment and excluded subjects with known congestive heart failure (CHF) and those with clinically defined bronchiectasis. The primary outcome was time to first AECOPD defined as “a complex of respiratory symptoms (increased or new onset) of more than one of the following: cough, sputum, wheezing, dyspnoea, or chest tightness with a duration of at least 3 days requiring treatment with antibiotics or systemic steroids” [2]. We monitored participants for AECOPDs at follow-up clinic visits …

Aclidinium bromide is a long-acting muscarinic antagonist approved for the long-term maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD). This 12-week phase III study evaluated efficacy and tolerability of aclidinium 200 or 400 μg in patients with moderate-to-severe COPD.In this double-blind study, 544 patients with COPD were randomized to placebo or twice-daily aclidinium 200 or 400 μg administered by Genuair(®)/Pressair(®). Lung function, health status [measured by the St. George's Respiratory Questionnaire (SGRQ)], dyspnea [measured using the Transition Dyspnea Index (TDI)], and safety were assessed throughout the study.Mean changes from baseline in morning trough forced expiratory volume in 1 s (FEV(1)) at week 12 (primary endpoint) were significantly higher for aclidinium than for placebo (200 μg, 51 mL; 400 μg, 72 mL; both p0.05). Aclidinium also significantly improved other lung function outcomes. At week 12, improvements from baseline were observed with aclidinium in SGRQ total score (200 μg, -6.0; 400 μg, -5.4) and TDI focal score (200 μg, 1.0; 400 μg, 1.3). Furthermore, clinically important improvements in SGRQ total and TDI focal scores were achieved by 45 and 51 % of patients, respectively, who received aclidinium 400 μg, with a significant difference versus placebo for TDI (p0.05). Anticholinergic-related adverse events (e.g., dry mouth) were infrequent, occurring2 % for any event in any treatment group. Both aclidinium doses were well tolerated.This study demonstrates efficacy and safety of aclidinium in COPD patients. Unexpected baseline imbalances between treatment groups may have impacted the aclidinium treatment benefit in this study.

Objectives (1) To assess the impact of American Thoracic Society and European Respiratory Society (ATS/ERS) ‘acceptability’ and ‘usability’ criteria for spirometry on the estimates of restrictive ventilatory defect in a population of taconite miners. (2) To compare estimates of restrictive ventilatory defect with three different pulmonary function tests (spirometry, alveolar volume (VA) and diffusing capacity (D L,CO )). (3) To assess the role of population characteristics on these estimates. Design Cross-sectional study. Setting Current and former workers in six current taconite mining operations of northeastern Minnesota were surveyed. Participants We attempted to enrol 3313 participants. Of these, 1353 responded while 1188 current and former workers fully participated in the survey and 1084 performed complete pulmonary function testing and were assessed. Primary and secondary outcome measures We applied ATS/ERS acceptability criteria for all tests and categorised participants into groups according to whether they fully met, partially met or did not meet acceptability criteria for spirometry. Obstruction and restriction were defined utilising the lower limit of normal for all tests. When using VA, restriction was identified after excluding obstruction. Results Only 519 (47.9%) tests fully met ATS/ERS spirometry acceptability criteria. Within this group, 5% had obstruction and 6%, restriction on spirometry. In contrast, among all participants (N=1084), 16.8% had obstruction, while 4.5% had restriction. VA showed similar results in all groups after obstruction was excluded. Impaired gas transfer (reduced D L,CO ) was identified in less than 50% of restriction identified by either spirometry or VA. Body mass index (BMI) was significantly related to spirometric restriction in all groups. Conclusions Population estimates of restriction using spirometry or VA varied by spirometric acceptability criteria. Other factors identified as important considerations in the estimation of restrictive ventilatory defect included increased BMI and gas transfer impairment in a relatively smaller proportion of those with spirometric restriction. These insights are important when interpreting population-based physiological data in occupational settings.

Background. Some patients are denied curative pulmonary resection for lung carcinoma because of pulmonary insufficiency. To identify factors that affect postoperative morbidity and mortality, we reviewed 85 consecutive patients (53 men and 32 women) with a preoperative forced expiratory volume in 1 second of less than 1.2 L who underwent pulmonary resection for lung cancer between January 1986 and December 1990. Methods. Median age was 70 years (range, 49 to 82 years). Sixty patients (71%) had been previously denied operation because of pulmonary insufficiency. Preoperative pulmonary function demonstrated a median preoperative forced expiratory volume in 1 second of 1.0 L (44% of predicted normal; range, 0.5 to 1.2 L) and a diffusing capacity of the lung for carbon monoxide of 60% of predicted normal (range, 22% to 104%). Results. Pneumonectomy was done in 6 patients (7.1%), bilobectomy in 6 (7.1%), lobectomy in 38 (44.7%), segmentectomy in 12 (14.1%), and wedge excision in 23 (27.1%). The median predicted postoperative forced ex piratory volume in 1 second was 0.83 L (34% of predicted normal; range, 0.45 to 1.14 L), and the median predicted postoperative diffusing capacity of the lung for carbon monoxide was 48% of predicted normal (range, 19% to 87%). Seventy-two patients (85%) received postoperative epidural analgesia. Median hospitalization was 15 days (range, 5 to 66 days). Operative mortality was 2.4%, and complications occurred in 49%. We did not identify any factors that predicted postoperative morbidity and mortality. Median follow-up was 3.2 years (range, 0.2 to 9 years). Seven patients (8%) required supplemental home oxygen. A predicted postoperative percent forced expiratory volume in 1 second less than 43% correlated with the need for home oxygen ( p Conclusions. We conclude that some patients with lung cancer and compromised pulmonary function can safely undergo pulmonary resection if selected appropriately.

In asthmatic and control subjects, we examined the changes in ventilatory capacity (VECap), end-expiratory lung volume (EELV), and degree of flow limitation during three types of exercise: 1) incremental, 2) constant load (50% of maximal exercise capacity; 36 min), and 3) interval (alternating between 60 and 40% of maximal exercise capacity; 6-min workloads for 36 min). The VECap and degree of flow limitation at rest and during the various stages of exercise were estimated by aligning the tidal breathing flow-volume (F-V) loops within the maximal expiratory F-V (MEFV) envelope using the measured EELV. In contrast to more usual estimates of VECap (i.e., maximal voluntary ventilation and forced expiratory volume in 1 s x 40), the calculated VECap depended on the existing bronchomotor tone, the lung volume at which the subjects breathed (i.e., EELV), and the tidal volume. During interval and constant-load exercise, asthmatic subjects experienced reduced ventilatory reserve, higher degrees of flow limitation, and had higher EELVs compared with nonasthmatic subjects. During interval exercise, the VECap of the asthmatic subjects increased and decreased with variations in minute ventilation, due in part to alterations in their MEFV curve as exercise intensity varied between 60 and 49% of maximal capacity. In conclusion, asthmatic subjects have a more variable VECap and reduced ventilatory reserve during exercise compared with nonasthmatic subjects. The variations in VECap are due in part to a more labile MEFV curve secondary to changes in bronchomotor tone. Asthmatics defend VECap and minimize flow limitation by increasing EELV.

Rationale: The course of lung function decline for smokers with early airflow obstruction remains undefined. It is also unclear which early spirometric characteristics identify individuals at risk for rapid decline and increased mortality.Objectives: To determine the association between spirometric measures and 5-year decline in FEV1 and 12-year mortality.Methods: We analyzed longitudinal data from the Lung Health Study, a clinical trial of intensive smoking cessation intervention with or without bronchodilator therapy in 5,887 smokers with mild to moderate airflow obstruction. Participants were stratified into bins of baseline FEV1 to FVC ratio, using bins of 5%, and separately into bins of Z-score (difference between actual and predicted FEV1/FVC, normalized to SD of predicted FEV1/FVC). Associations between spirometric measures and FEV1 decline and mortality were determined after adjusting for baseline characteristics and time-varying smoking status.Measurements and Main Results: The cohort was approxi...

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Chronic obstructive pulmonary disease (COPD) is a strong risk factor for lung cancer. Published studies about variations of genes encoding glutathione metabolism, DNA repair, and inflammatory response pathways in susceptibility to COPD were inconclusive. We evaluated 470 single-nucleotide polymorphisms (SNP) from 56 genes of these three pathways in 620 cases and 893 controls to identify susceptibility markers for COPD risk, using existing resources. We assessed SNP- and gene-level effects adjusting for sex, age, and smoking status. Differential genetic effects on disease risk with and without lung cancer were also assessed; cumulative risk models were established. Twenty-one SNPs were found to be significantly associated with risk of COPD (P < 0.01); gene-based analyses confirmed two genes (GCLC and GSS) and identified three additional genes (GSTO2, ERCC1, and RRM1). Carrying 12 high-risk alleles may increase risk by 2.7-fold; eight SNPs altered COPD risk without lung cancer by 3.1-fold and 4 SNPs altered the risk with lung cancer by 2.3-fold. Our findings indicate that multiple genetic variations in the three selected pathways contribute to COPD risk through GCLC, GSS, GSTO2, ERCC1, and RRM1 genes. Functional studies are needed to elucidate the mechanisms of these genes in the development of COPD, lung cancer, or both. Cancer Prev Res; 5(3); 365–73. ©2011 AACR.

Leukotrienes have been implicated in the pathogenesis of acute exacerbations of COPD, but leukotriene modifiers have not been studied as a possible therapy for exacerbations.We sought to test the safety and efficacy of adding oral zileuton (a 5-lipoxygenase inhibitor) to usual treatment for acute exacerbations of COPD requiring hospitalization.Randomized double-blind, placebo-controlled, parallel group study of zileuton 600 mg orally, 4 times daily versus placebo for 14 days starting within 12 hours of hospital admission for COPD exacerbation. Primary outcome measure was hospital length of stay; secondary outcomes included treatment failure and biomarkers of leukotriene production.Sixty subjects were randomized to zileuton and 59 to placebo (the study was stopped short of enrollment goals because of slow recruitment). There was no difference in hospital length of stay (3.75 +/- 2.19 vs. 3.86 +/- 3.06 days for zileuton vs. placebo, p = 0.39) or treatment failure (23% vs. 27% for zileuton vs. placebo, p = 0.63) despite a decline in urinary LTE(4) levels in the zileuton-treated group as compared to placebo at 24 hours (change in natural log-transformed ng/mg creatinine -1.38 +/- 1.19 vs. 0.14 +/- 1.51, p0.0001) and 72 hours (-1.32 +/- 2.08 vs. 0.26 +/- 1.93, p0.006). Adverse events were similar in both groups.While oral zileuton during COPD exacerbations that require hospital admission is safe and reduces urinary LTE(4) levels, we found no evidence suggesting that this intervention shortened hospital stay, with the limitation that our sample size may have been insufficient to detect a modest but potentially meaningful clinical improvement.

The nonspecific (NS) pulmonary function (PF) pattern refers to a PF test with a normal total lung capacity (TLC), normal FEV₁/FVC ratio, and a low FEV₁, a low FVC, or both. Currently, no information is available regarding the long-term stability of the NS pattern or variables that predict changes in subjects with an initial NS PF pattern.From 1990 to 2005 we identified 1,284 subjects with an NS pattern on initial PF testing with one or more follow-up PF tests 6 months or more after the initial NS test result. Lung volumes, diffusing capacity, and spirometry data were analyzed. A multivariate, multinomial logistic regression model was used to study the association between different variables and the final PF pattern.Overall, 3,674 PF tests were performed in 1,284 subjects over a median follow-up period of 3 years. At last follow-up, 818/1,284 (64%) subjects continued to show the NS pattern, whereas 208/1,284 (16%) showed a restrictive pattern, 191/1,284 (15%) an obstructive pattern, 42/1,284 (3%) a normal pattern, and 25/1,284 (2%) a mixed pattern. The multinomial logistic regression analysis showed that increasing values for specific airway resistance and the difference between TLC and alveolar volume were predictors of a change to an obstructive pattern on follow-up.The NS pattern is a distinct and stable PF test pattern with roughly two-thirds of patients continuing to show this pattern on follow-up testing. Current interpretation guidelines erroneously label the NS pattern as representing obstruction and need to be changed to reflect these data.

COPD is common in patients undergoing percutaneous coronary intervention (PCI), but its association with outcomes following PCI has received only limited study. The effects of COPD severity on outcomes after PCI are not known.We conducted a retrospective cross-sectional analysis of prospectively acquired data in 14,346 consecutive patients enrolled in the Mayo Clinic PCI registry. Patients with COPD were identified by International Classification of Diseases, 9th edition, coding and pulmonary function test (PFT) results. Outcomes of COPD vs non-COPD cohorts were compared.The COPD group included 2,001 patients (72% men) aged 70 +/- 10 years, and the non-COPD group included 12,345 patients (70% men) aged 66 +/- 12 years. In the follow-up period after PCI (median, 4.1 years; interquartile range, 1.9-7.0 years), the patients with COPD experienced a significantly higher incidence of all-cause mortality (P.0001), cardiac mortality (P.0001), and myocardial infarction (MI) (P.0001) than the patients without COPD. Additionally, severity of COPD was associated with increased mortality after PCI (P.0001). In a multivariate analysis, COPD presence and severity remained significant risk factors for mortality (P.0001), cardiac mortality (P.0001), and occurrence of MI after PCI (P.0001).COPD is associated with significantly increased overall long-term mortality, cardiac mortality, and occurrence of MI in patients undergoing PCI. Increasing severity of COPD as measured by PFT is associated with decreased survival after PCI. Screening for COPD in patients undergoing PCI could contribute importantly to risk stratification, identifying patients needing closer follow-up and optimizing targeted therapeutic interventions.

Patients with severe chronic obstructive pulmonary disease (COPD) may have varying levels of disability despite similar levels of lung function. This variation may reflect different COPD subtypes, which may have different genetic predispositions.To identify genetic associations for COPD-related phenotypes, including measures of exercise capacity, pulmonary function, and respiratory symptoms.In 304 subjects from the National Emphysema Treatment Trial, we genotyped 80 markers in 22 positional and/or biologically plausible candidate genes. Regression models were used to test for association, using a test-replication approach to guard against false-positive results. For significant associations, effect estimates were recalculated using the entire cohort. Positive associations with dyspnea were confirmed in families from the Boston Early-Onset COPD Study.The test-replication approach identified four genes-microsomal epoxide hydrolase (EPHX1), latent transforming growth factor-beta binding protein-4 (LTBP4), surfactant protein B (SFTPB), and transforming growth factor-beta1 (TGFB1)-that were associated with COPD-related phenotypes. In all subjects, single-nucleotide polymorphisms (SNPs) in EPHX1 (por = 0.03) and in LTBP4 (por = 0.03) were associated with maximal output on cardiopulmonary exercise testing. Markers in LTBP4 (por = 0.05) and SFTPB (p = 0.005) were associated with 6-min walk test distance. SNPs in EPHX1 were associated with carbon monoxide diffusing capacity (por = 0.04). Three SNPs in TGFB1 were associated with dyspnea (por = 0.002), one of which replicated in the family study (p = 0.02).Polymorphisms in several genes seem to be associated with COPD-related traits other than FEV(1). These associations may identify genes in pathways important for COPD pathogenesis.

Inhaled glucocorticosteroids (ICS) are commonly prescribed for chronic obstructive pulmonary disease. No adverse effect on bone mineral density (BMD) has been proven. In a randomized double-blind, placebo-controlled trial at seven centers in North America, we recruited 412 current smokers or recent quitters with mild to moderate chronic obstructive pulmonary disease. They used inhaled triamcinolone acetonide, 600 mcg, or placebo, twice daily. We measured femoral neck and lumbar spine BMD at baseline and after 1 and 3 years, and serum osteocalcin at baseline, 3 months, 1 year, and 3 years. After 3 years, BMD at the femoral neck decreased 1.78% more with ICS than with placebo (p0.001). More participants in the ICS group experienced 6% or more loss of femoral neck BMD (p = 0.002). Lumbar spine BMD increased in the placebo group by 0.98% but decreased by 0.35% in the ICS group (a difference of 1.33%, p = 0.007). Changes in osteocalcin did not correlate with changes in BMD. Fractures, lost height, or osteoporosis diagnoses were not increased among ICS users compared with placebo users. In summary, the use of inhaled triamcinolone acetonide was associated with loss of BMD at the femoral neck and lumbar spine after 3 years of treatment.

Single-breath diffusing capacity of the lung for carbon monoxide (DLCO) is used as a pulmonary function test (PFT) to assess gas transfer in the lungs. The implications of a low DLCO are well-recognized, but the clinical significance of a high DLCO is not clear. The aim of this study was to identify the clinical correlates of a high DLCO.We identified 245 patients with a high DLCO (ie,140% predicted) and a matched group of 245 patients with normal DLCO (ie, 85 to 115% predicted), who were selected from a laboratory database of 45,000 patients tested between January 1997 and December 1999. We compared the demographic features, clinical diagnoses, and PFT data between the two groups.Large multispecialty group practice.The patients in the high DLCO group were heavier (mean [+/- SD] weight, 96.0 +/- 22.9 vs 85.0 +/- 21.3 kg, respectively; p0.001), had a higher mean body mass index (32.9 +/- 7.4 vs 29.4 +/- 6.4 kg/m(2), respectively; p0.001), larger body surface area (p0.001), and larger mean total lung capacity (p = 0.007) and alveolar volume (p0.001). The clinical diagnoses of obesity (p0.001) and asthma (p0.001) were more common among patients with high DLCO values. The majority of patients (62%) with a high DLCO had a diagnosis of obesity, asthma, or both. Polycythemia, hemoptysis, and left-to-right shunt were uncommon.A high DLCO on a PFT is most frequently associated with large lung volumes, obesity, and asthma. Other conditions are much less common. A clinical condition, which typically reduces DLCO, may deceptively normalize DLCO in such patients.

More than 30 million Americans have chronic obstructive pulmonary disease (COPD) and asthma, with internists, pediatricians, and family physicians providing most of their medical care. Recent management guidelines for asthma and COPD recommend regular use of spirometry for the diagnosis and management of these disorders. Because of the development of easy-to-use office-based spirometers, an increasing number of physicians have ready access to spirometry. Beyond simple spirometry, various tests are available from many pulmonary function laboratories for more detailed evaluation of patients with respiratory disorders. For these reasons, all physicians who care for patients with pulmonary disease must understand basic pulmonary function testing and have a fundamental understanding of more sophisticated tests. A series of performance standards has been developed for improved accuracy and precision of pulmonary function tests. Physicians responsible for administering and interpreting pulmonary function tests, even simple spirometry, must be aware of relevant guidelines. This concise review addresses current indications for pulmonary function testing, provides an overview of the studies commonly available in modern pulmonary function laboratories, and includes comments on basic interpretation and testing standards.

Inhaled corticosteroids (ICS) are widely used in the treatment of COPD. One of the potential adverse effects of their use is the development of adrenal suppression. Our study aimed to determine the effects of ICS on adrenal function over 3 years of use in patients with COPD.Two hundred twenty-one subjects were recruited from the 1,116 patients already enrolled in Lung Health Study II and were randomized to receive either triamcinolone, 1,200 microg, or placebo daily. Basal cortisol levels and cortisol levels at 30 min and 60 min following cosyntropin injection were measured at study entry and after 1 year and 3 years of participation.Basal cortisol levels in the placebo group were higher than in those receiving active drug at all time points and rose through the study period. There was no suppression of cortisol levels after cosyntropin stimulation at any study point in any subgroup.Use of inhaled triamcinolone, 1,200 microg/d, over 3 years does not suppress baseline adrenal function or diminish adrenal responsiveness to cosyntropin stimulation.

Background Asthma is the most common chronic condition of childhood and a common reason for school absenteeism and use of school health services. Unrecognized but symptomatic childhood asthma may be adding to this school burden. Objective To evaluate the effectiveness of school-based asthma screening in identifying children at high risk for unrecognized asthma and facilitating new asthma diagnoses. Methods A controlled trial of school-based asthma screening using mailed parent surveys and medical record review to estimate outcomes of interest, specifically numbers of new asthma diagnoses. Results Most parents (80%, N = 5116) responded to the asthma screening survey. About 1 in 5 (19.4%, n = 994) parents reported that their children had previously been diagnosed with asthma or reactive airway disease. Letters recommending further evaluation for symptoms suggestive of possible asthma were sent to the parents of 388 children (7.6% of respondents) without known asthma. About half of parents returned postcards stating their intended reaction to the referral recommendation including 52 parents (13.4% of those referred) who thought no further action was necessary. Parent-initiated physician visits occurred in 45 (11.6%) of the 388 referred children. Overall, there were 57 (0.9%, 57/6401) new physician diagnoses of asthma among the screened children in the 6 months following screening: 16 in the referred group and 41 in the group not referred, including 20 in the group whose parents said they had known that their child had asthma, but had no medical record documentation of an asthma diagnosis. The incident asthma diagnosis rate was 1.2% (34/2906; P = .25) in a comparable control group that did not participate in screening. Conclusions School-based asthma screening did not increase the incident rate of asthma diagnoses in this community. Parents participated in the screening process, but the percentage of referred children with follow-up medical visits was low.

A matched case-controlled study was conducted to determine if airway obstruction or emphysema were associated with an increased risk of lung cancer. Lung cancer cases (n=24) were identified through a low-dose spiral computed tomography (CT) screening trial from 1,520 participants. Four controls without lung cancer were selected for each case from the participants and matched by sex, age and smoking history. Emphysema was assessed by quantitative CT analysis. Conditional logistic regression was employed to assess results of spirometry and CT quantitative analysis as potential risk factors for lung cancer. The likelihood of lung cancer was found to be significantly increased for those with forced expiratory volume in one second (FEV1) < or = 40% of predicted. The results suggested that a lower percentage of predicted FEV1 was indicative of lung cancer. No compelling evidence was found to suggest that the percentage of emphysema was associated with lung cancer. These results suggest an increased risk of lung cancer associated with airway obstruction. However, percentage of emphysema as determined by computed tomography was not associated with an increased risk of lung cancer.

Objective: Using a unique county-wide resource that links all health care providers' medical records to assess current and "ever" prevalence of physician-diagnosed asthma. To describe the age and sex rates and temporal trends in new asthma diagnoses and associations with race and socio-economic status. Study design: A longitudinal retrospective evaluation of a population-based cohort of school children using linked medical and school records. Results: Overall, 17.6% of children in grades kindergarten through 12 had a physician diagnosis of asthma and 12.9% had an asthma-related visit within the past 2 years. An additional 19.7% had visits for reactive airway disease or recurrent wheezing or bronchospasm with no diagnosis of asthma. Children provided with free and reduced-cost lunches had lower cumulative and incident asthma rates from birth through their current school age. Race was not related to rates of physician-diagnosed asthma. There was a significant temporal increase in rates of new asthma diagnoses. Conclusions: In this community, 1 in 3 children have had a physician-documented recurrent wheezing-type illness, and 1 in 6 were diagnosed with asthma. Diagnoses rates were directly related to socioeconomic status. (J Pediatr 2002;140:576-81)

Importance Previous studies suggest cross-sectional associations between a diagnosis of chronic obstructive pulmonary disease (COPD) and mild cognitive impairment (MCI). However, few studies have assessed whether COPD, a potentially modifiable factor, is associated with an increased risk for MCI and whether the relation is specific to the type of MCI. Objective To investigate whether a diagnosis of COPD and duration of COPD are associated with an increased risk for incident MCI and MCI subtypes (amnestic MCI [A-MCI] and nonamnestic MCI [NA-MCI]). Design, Setting, and Participants A prospective population-based cohort from the Mayo Clinic Study on Aging. We included 1425 cognitively normal individuals aged 70 to 89 years who were randomly selected from Olmsted County, Minnesota, on October 1, 2004, using the medical records linkage system. At baseline and every 15 months thereafter, participants underwent assessment with a nurse interview, neurologic examination, and neuropsychological testing. A diagnosis of COPD was confirmed via medical record review. A baseline diagnosis of COPD and duration of COPD were examined as risk factors for MCI and MCI subtypes using Cox proportional hazards models and adjusting for demographic variables and medical comorbidities, with age as the time scale. Exposure A baseline diagnosis of COPD and duration of COPD. Main Outcomes and Measures Incident MCI, A-MCI, and NA-MCI. Results Of the 1425 participants with normal cognition at baseline, 370 developed incident MCI. The median duration of follow-up was 5.1 years (interquartile range, 3.8-5.4 years). A diagnosis of COPD significantly increased the risk for NA-MCI by 83% (hazard ratio, 1.83 [95% CI, 1.04-3.23]), but not of any MCI or A-MCI in multivariate analyses. We found a dose-response relationship such that individuals with COPD duration of longer than 5 years at baseline had the greatest risk for any MCI (hazard ratio, 1.58 [95% CI, 1.04-2.40]) and NA-MCI (2.58 [1.32-5.06]). Conclusions and Relevance A diagnosis of COPD is associated with an increased risk for MCI, particularly NA-MCI. We have found a dose-response relationship between COPD duration and risk for MCI. These findings highlight the importance of COPD as a risk factor for MCI and may provide a substrate for early intervention to prevent or delay the onset and progression of MCI, particularly NA-MCI.

BACKGROUND Chronic obstructive pulmonary disease (COPD) results from a progressive decline in lung function, which is thought to be the consequence of airway inflammation. We hypothesized that antiinflammatory therapy with inhaled corticosteroids would slow this decline. METHODS We enrolled 1116 persons with COPD whose forced expiratory volume in one second (FEV1) was 30 to 90 percent of the predicted value in a 10-center, placebo-controlled, randomized trial of inhaled triamcinolone acetonide administered at a dose of 600 microg twice daily. The primary outcome measure was the rate of decline in FEV1 after the administration of a bronchodilator. The secondary outcome measures included respiratory symptoms, use of health care services, and airway reactivity. In a substudy of 412 participants, we measured bone density in the lumbar spine and femur at base line and one and three years after the beginning of treatment. RESULTS The mean duration of follow-up was 40 months. The rate of decline in the FEV1 after bronchodilator use was similar in the 559 participants in the triamcinolone group and the 557 participants in the placebo group (44.2+/-2.9 vs. 47.0+/-3.0 ml per year, P= 0.50). Members of the triamcinolone group had fewer respiratory symptoms during the course of the study (21.1 per 100 person-years vs. 28.2 per 100 person-years, P=0.005) and had fewer visits to a physician because of a respiratory illness (1.2 per 100 person-years vs. 2.1 per 100 person-years, P=0.03). Those taking triamcinolone also had lower airway reactivity in response to methacholine challenge at 9 months and 33 months (P=0.02 for both comparisons). After three years, the bone density of the lumbar spine and the femur was significantly lower in the triamcinolone group (P < or = 0.007). CONCLUSIONS Inhaled triamcinolone does not slow the rate of decline in lung function in people with COPD, but it improves airway reactivity and respiratory symptoms and decreases the use of health care services for respiratory problems. These benefits should be weighed against the potential long-term adverse effects of triamcinolone on bone mineral density.

Tests of pulmonary function and radiographic imaging of the chest are the two key methods used in diagnostic evaluation of patients with pulmonary disease. Unlike blood pressure, acceptable normal values vary from person to person and from one demographic group to another. The first studies, in 1846, of spirometric assessment of forced vital capacity (FVC), the most basic pulmonary-function test, showed that normal values for vital capacity vary as a function of height and age.1 A few years later, it was shown that vital capacity was 6 to 12% lower in healthy black soldiers than in white or Native American . . .