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BACKGROUND: Persistent impairment of pulmonary function and exercise capacity has been known to last for months or even years in the survivors who recovered from other coronavirus pneumonia. Some reports showed that subjects with coronavirus disease 2019 pneumonia after being discharged could have several sequelae, but there are few studies on gas exchange and exercise capacity complications in these subjects. AIMS: To describe residual gas exchange abnormalities during recovery from coronavirus disease 2019 pneumonia. METHODS: In an observational study, ∼90 d after onset of disease, we scheduled almost 200 subjects for an out-patient visit with pulmonary function testing and computed tomography of the lungs. Lung mechanics by using body plethysmography, gas exchange with diffusing lung capacity for carbon monoxide determined by the single-breath technique (DLCOsb) and diffusing lung capacity for nitric oxide determined by the single-breath technique (DLNOsb), and exercise ability by using the 6-min walk test (6MWT) were measured in the subjects. The results were compared between those who required invasive mechanical ventilation and those who did not. RESULTS: A total of 171 subjects were included, the majority (96%) had signs of residual pneumonia (such as an excess of high attenuation areas) on computed tomography of the lungs. The DLCOSB results were below the lower limit of the normal range in 29.2% of the subjects; during the 6MWT, 67% experienced oxygen desaturation ( S pO 2 ) > 4%; and, in 81 (47%), the dropped below 88%. Subjects who required invasive mechanical ventilation (49.7%) were more likely to have lower lung volumes, more gas exchange abnormality, less exercise capacity and more radiologic abnormality. CONCLUSIONS: Subjects who recovered from severe COVID-19 pneumonia continued to have abnormal lung function and abnormal radiologic findings.

Chronic lower respiratory diseases (CLRDs) are the fourth leading cause of death in the United States. To support investigations into CLRD risk determinants and new approaches to primary prevention, we aimed to harmonize and pool respiratory data from US general population-based cohorts. Data were obtained from prospective cohorts that performed prebronchodilator spirometry and were harmonized following 2005 ATS/ERS standards. In cohorts conducting follow-up for noncardiovascular events, CLRD events were defined as hospitalizations/deaths adjudicated as CLRD-related or assigned relevant administrative codes. Coding and variable names were applied uniformly. The pooled sample included 65,251 adults in 9 cohorts followed-up for CLRD-related mortality over 653,380 person-years during 1983-2016. Average baseline age was 52 years; 56% were female; 49% were never-smokers; and racial/ethnic composition was 44% white, 22% black, 28% Hispanic/Latino, and 5% American Indian. Over 96% had complete data on smoking, clinical CLRD diagnoses, and dyspnea. After excluding invalid spirometry examinations (13%), there were 105,696 valid examinations (median, 2 per participant). Of 29,351 participants followed for CLRD hospitalizations, median follow-up was 14 years; only 5% were lost to follow-up at 10 years. The NHLBI Pooled Cohorts Study provides a harmonization standard applied to a large, US population-based sample that may be used to advance epidemiologic research on CLRD.

Rationale: Accurate reference values for spirometry are important because the results are used for diagnosing common chronic lung diseases such as asthma and chronic obstructive pulmonary disease, estimating physiologic impairment, and predicting all-cause mortality. Reference equations have been established for Mexican Americans but not for others with Hispanic/Latino backgrounds.Objectives: To develop spirometry reference equations for adult Hispanic/Latino background groups in the United States.Methods: The HCHS/SOL (Hispanic Community Health Study/Study of Latinos) recruited a population-based probability sample of 16,415 Hispanics/Latinos aged 18–74 years living in the Bronx, Chicago, Miami, and San Diego. Participants self-identified as being of Puerto Rican, Cuban, Dominican, Mexican, or Central or South American background. Spirometry was performed using standardized methods with central quality control monitoring. Spirometric measures from a subset of 6,425 never-smoking participants without resp...

BACKGROUND: The 2005 American Thoracic Society/European Respiratory Society guidelines for single-breath diffusing capacity of the lung for carbon monoxide (DLCO) recommend a weekly biological control test and/or DLCO simulator to detect instrument error drift. Very little has been published regarding the results of such a quality assurance program. Our aim was to analyze the long-term stability of a portable DLCO instrument. METHODS: We used a new EasyOne Pro system and checked its accuracy using a DLCO simulator with 2 reference gases (concentration A: carbon monoxide [CO] = 0.1% and helium = 6.52%; concentration B: CO = 0.08% and helium = 7.21%) during the first 3 y of use in our large clinical laboratory. To detect instrument drift, a healthy woman (MSC), age 43 y old at baseline, tested herself every week during this period of time. RESULTS: More than 6,000 spirometry and 5,000 DLCO maneuvers were done using this instrument for patients during these 3 y. There were no failures in the daily volume and flow checks or the CO and helium calibration checks performed automatically by the instrument. The differences between the simulator DLCO and the measured DLCO were −0.91 ± 1.33 mL/min/mm Hg and −0.61 ± 1.45 mL/min/mm Hg for concentration A and concentration B, respectively. The results of the 110 biological control tests were: mean 30.8 ± 1.7 mL/min/mm Hg (95% CI 30.5–31.1), coefficient of variation of 5.4% in DLCO, and repeatability of 2.5 mL/min/mm Hg. Only 4 measurements were outside ±3 mL/min/mm Hg (3.6%). Her mean alveolar volume was 4.2 ± 0.25 L with coefficient of variation of 6.2%; her inspired volume was 3.05 ± 0.14 L, and coefficient of variation = 4.5%. CONCLUSIONS: Measurements of DLCO were stable over the 3-y period without any need for manual recalibration of the instrument. The biological control was as good as the DLCO simulator to evaluate this kind of device in a long-term laboratory quality control program.

Measurement of diffusing capacity of the lungs for carbon monoxide (DLCO), also known as transfer factor, is the second most important pulmonary function test (PFT), after spirometry. Previously available only in hospital-based PFT labs, DLCO testing is now available at outpatient clinics using a portable device. Compared to spirometry tests, assessments with these devices require very little effort. The patient breathes quietly, inhales the test gas, holds the breath for ten seconds, and then exhales. In adult smokers with post-bronchodilator airway obstruction, a low DLCO greatly increases the probability of the emphysema phenotype of COPD due to cigarette smoking, while a normal DLCO makes chronic asthma more likely. In patients with spirometric restriction (a low FVC with a normal FEV1/FVC), a low DLCO increases the pre-test probability of an interstitial lung disease (ILD), while a normal DLCO makes a chest wall type of restriction more likely. A normal TLC (VA from the single-breath helium dilution provided by a DLCO test) rules out restriction of lung volumes without the need for a body box measurement. In patients with dyspnea of unknown cause, the pattern of a low DLCO with normal spirometry increases the likelihood of pulmonary vascular disease, but this pattern also occurs with several other diseases such as a mild ILD. Once a diagnosis is made, the percent predicted DLCO provides an objective index of disease severity and prognosis. A DLCO below 40% predicted, or a decline in DLCO of more than 4 units, is associated with increased morbidity and mortality.

Evidence suggests that lung injury, inflammation and extracellular matrix remodelling precede lung fibrosis in interstitial lung disease (ILD). We examined whether a quantitative measure of increased lung attenuation on computed tomography (CT) detects lung injury, inflammation and extracellular matrix remodelling in community-dwelling adults sampled without regard to respiratory symptoms or smoking.We measured high attenuation areas (HAA; percentage of lung voxels between −600 and −250 Hounsfield Units) on cardiac CT scans of adults enrolled in the Multi-Ethnic Study of Atherosclerosis.HAA was associated with higher serum matrix metalloproteinase-7 (mean adjusted difference 6.3% per HAA doubling, 95% CI 1.3–11.5), higher interleukin-6 (mean adjusted difference 8.8%, 95% CI 4.8–13.0), lower forced vital capacity (FVC) (mean adjusted difference −82 mL, 95% CI −119–−44), lower 6-min walk distance (mean adjusted difference −40 m, 95% CI −1–−80), higher odds of interstitial lung abnormalities at 9.5 years (adjusted OR 1.95, 95% CI 1.43–2.65), and higher all cause-mortality rate over 12.2 years (HR 1.58, 95% CI 1.39–1.79).High attenuation areas are associated with biomarkers of inflammation and extracellular matrix remodelling, reduced lung function, interstitial lung abnormalities, and a higher risk of death among community-dwelling adults.

Emphysema on CT is associated with accelerated lung function decline in heavy smokers and patients with COPD; however, in the general population, it is not known whether greater emphysema-like lung on CT is associated with incident COPD. We used data from 2045 adult participants without initial prebronchodilator airflow limitation, classified by FEV1/FVC>upper limit of normal, was associated with increased odds of incident airflow limitation at 5-year follow-up on both prebronchodilator (adjusted OR 2.62, 95% CI 1.47 to 4.67) and postbronchodilator (adjusted OR 4.38, 95% CI 1.63 to 11.74) spirometry, independent of smoking history. These results support investigation into whether emphysema-like lung could be informative for COPD risk stratification.

Rationale: Genome-wide association studies (GWAS) of chronic obstructive pulmonary disease (COPD) have identified disease-susceptibility loci, mostly in subjects of European descent.Objectives: We hypothesized that by studying Hispanic populations we would be able to identify unique loci that contribute to COPD pathogenesis in Hispanics but remain undetected in GWAS of non-Hispanic populations.Methods: We conducted a metaanalysis of two GWAS of COPD in independent cohorts of Hispanics in Costa Rica and the United States (Multi-Ethnic Study of Atherosclerosis [MESA]). We performed a replication study of the top single-nucleotide polymorphisms in an independent Hispanic cohort in New Mexico (the Lovelace Smokers Cohort). We also attempted to replicate prior findings from genome-wide studies in non-Hispanic populations in Hispanic cohorts.Measurements and Main Results: We found no genomewide significant association with COPD in our metaanalysis of Costa Rica and MESA. After combining the top results from this metaanalysis with those from our replication study in the Lovelace Smokers Cohort, we identified two single-nucleotide polymorphisms approaching genome-wide significance for an association with COPD. The first (rs858249, combined P value = 6.1 X 10(-8)) is near the genes KLHL7 and NUPL2 on chromosome 7. The second (rs286499, combined P value = 8.4 X 10(-8)) is located in an intron of DLG2. The two most significant single-nucleotide polymorphisms in FAM13A from a previous genome-wide study in non-Hispanics were associated with COPD in Hispanics.Conclusions: We have identified two novel loci (in or near the genes KLHL7/NUPL2 and DLG2) that may play a role in COPD pathogenesis in Hispanic populations.

BACKGROUND: Some technologists worry that patients with very severe lung disease are unable to complete several spirometry maneuvers, which require considerable effort. METHODS: We retrospectively selected all spirometry tests with an FEV1 < 35% predicted done by adult subjects sent to our pulmonary function laboratory during a 3-y period. We determined the rates and correlates of poor quality test sessions. RESULTS: Approximately 90% of the tests done by the 558 subjects with very severe lung-function impairment (of > 30,000 subjects tested during the 3-y period) had adequate quality spirometry. Subjects with airway obstruction were less likely to meet FVC repeatability goals. A poor spirometry quality grade was associated with a very low FVC and a low body mass index, but not older age. CONCLUSIONS: Severe lung disease should not be used as an excuse for not meeting spirometry quality goals.

Chronic lower respiratory diseases (CLRDs) are the fourth leading cause of death in the United States. To support investigations into CLRD risk determinants and new approaches to primary prevention, we aimed to harmonize and pool respiratory data from US general population-based cohorts. Data were obtained from prospective cohorts that performed prebronchodilator spirometry and were harmonized following 2005 ATS/ERS standards. In cohorts conducting follow-up for noncardiovascular events, CLRD events were defined as hospitalizations/deaths adjudicated as CLRD-related or assigned relevant administrative codes. Coding and variable names were applied uniformly. The pooled sample included 65,251 adults in 9 cohorts followed-up for CLRD-related mortality over 653,380 person-years during 1983–2016. Average baseline age was 52 years; 56% were female; 49% were never-smokers; and racial/ethnic composition was 44% white, 22% black, 28% Hispanic/Latino, and 5% American Indian. Over 96% had complete data on smoking, clinical CLRD diagnoses, and dyspnea. After excluding invalid spirometry examinations (13%), there were 105,696 valid examinations (median, 2 per participant). Of 29,351 participants followed for CLRD hospitalizations, median follow-up was 14 years; only 5% were lost to follow-up at 10 years. The NHLBI Pooled Cohorts Study provides a harmonization standard applied to a large, US population-based sample that may be used to advance epidemiologic research on CLRD.

BACKGROUND: Measured maximum voluntary ventilation (MVV) correlates with maximum ventilatory capacity during exercise. As a shortcut, MVV is often estimated by multiplying measured FEV 1 times 35 or 40, but this index varies with altitude due to reduced air density. The objective was to describe MVV in healthy individuals residing at 2,240 m above sea level and compare it with the reference values customarily employed. METHODS: We recruited a convenience sample of respiratory-healthy, non-obese volunteers >10 y of age who had resided for >2 y in Mexico City. All participants performed forced spirometry and MVV according to current standards. Multiple regression models were fitted, including age, height, and measured FEV 1 , separately for males and females to obtain reference values. The impact of lower air density on MVV at this elevation was estimated from the reported increase in peak flow in relation to altitude. RESULTS: We studied 381 individuals (210 females [55.1%]) age 10–80 y with a mean MVV of 145.6 ± 48 L/min. Both FEV 1 × 35 and FEV 1 × 40 underestimated the MVV observed: in males by approximately 26% and in females by approximately 10%. MVV for our population approached FEV 1 × 45 (98 ± 15.6% of real MVV). Multiple regression models including height, weight, and measured FEV 1 explained 70% of residual variability once sex was taken into account. CONCLUSIONS: At an altitude of 2,240 m, MVV is about 45 times the measured FEV 1 , and it can be estimated for other altitudes. The best predicting equations for MVV were calculated separately for females and males and included the following predictors: age, age 2 , and measured FEV 1 . The study found that reference values for MVV from studies conducted at sea level are inaccurate at this altitude.

Objective: To examine the association between 6-min walk test (6 MWT) performance and all-cause mortality, coronary heart disease mortality, and incident coronary heart disease in older adults. Method: We conducted a time-to-event analysis of 1,665 Cardiovascular Health Study participants without prevalent cardiovascular disease with a 6 MWT. Results: During a mean follow-up of 8 years, there were 305 incident coronary heart disease events, and 504 deaths of which 100 were coronary heart disease–related deaths. The 6 MWT performance in the shortest two distance quintiles was associated with increased risk of all-cause mortality (290-338 m: hazard ratio [HR] = 1.7; 95% confidence interval [CI] = [1.2, 2.5]

Almost every hospital-based pulmonary function laboratory (PFT lab) uses a body plethysmograph (body box) to measure static lung volumes (total lung capacity [TLC], functional residual capacity [FR...

Chronic obstructive pulmonary disease (COPD) is linked to cardiovascular disease; however, there are few studies on the associations of cardiovascular genes with COPD. We assessed the association of lung function with 2,100 genes selected for cardiovascular diseases among 20,077 European-Americans and 6,900 African-Americans. We performed replication of significant loci in the other racial group and an independent consortium of Europeans, tested the associations of significant loci with percent emphysema, and examined gene expression in an independent sample. We then tested the association of a related lipid biomarker with FEV1/FVC and percent emphysema. We identified one new polymorphism for FEV1/FVC (rs805301) in European-Americans (p=1.3×10−6) and a second (rs707974) in the combined European-American and African-American analysis (p=1.38×10−7). Both SNPs flank the gene for apolipoprotein M (apoM), a component of HDL. Both replicated in an independent cohort. SNPs in a second gene related to apoM and HDL, PCSK9 , were associated with FEV1/FVC among African-Americans. rs707974 was associated with percent emphysema among European-Americans and African-Americans, and APOM expression was related to FEV1/FVC and percent emphysema. Higher HDL levels were associated with lower FEV1/FVC and greater percent emphysema. These findings suggest a novel role for the APOM/HDL pathway in the pathogenesis of COPD and emphysema.

Background Severe COPD can lead to cor pulmonale and emphysema and is associated with impaired left ventricular (LV) filling. We evaluated whether emphysema and airflow obstruction would be associated with changes in right ventricular (RV) structure and function and whether these associations would differ by smoking status. Methods The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRI on 5,098 participants without clinical cardiovascular disease aged 45 to 84 years. RV and emphysema measures were available for 4,188 participants. Percent emphysema was defined as the percentage of voxels below −910 Hounsfield units in the lung windows on cardiac CT scans. Generalized additive models were used to control for confounders and adjust for respective LV parameters. Results Participants consisted of 13% current smokers, 36% former smokers, and 52% never smokers. Percent emphysema was inversely associated with RV end-diastolic volume, stroke volume, cardiac output, and mass prior to adjustment for LV measures. After adjustment for LV end-diastolic volume, greater percent emphysema was associated with greater RV end-diastolic volume (+1.5 mL, P = .03) among current smokers, smaller RV end-diastolic volume (−0.8 mL, P = .02) among former smokers, and similar changes among never smokers. Conclusions Percent emphysema was associated with smaller RV volumes and lower mass. The relationship of emphysema to cardiac function is complex but likely involves increased pulmonary vascular resistance, predominantly with reduced cardiac output, pulmonary hyperinflation, and accelerated cardiopulmonary aging.

We welcome the important paper by Grønseth et al. [1], which used data from the Burden of Obstructive Lung Disease (BOLD) project to highlight the prevalence of breathlessness across the world. As well as being significant because it is a source of suffering that should be ameliorated, we believe that attention to breathlessness, particularly in midlife, has important implications for sustainable healthcare because it allows timely diagnosis, would drive the promotion of physical activity, forms part of a strategy to reduce the burden of comorbidities and would have beneficial environmental effects., Targeting breathlessness is important for delivering sustainable future healthcare http://ow.ly/AgKoA

6MWD: patients who desaturate have higher morbidity/mortality rates when compared with those who do not desaturatehttp://ow.ly/J63B3006JCg

One in 12 adults has chronic obstructive pulmonary disease or asthma. Acute exacerbations of these chronic lower respiratory diseases (CLRDs) are a major cause of morbidity and mortality. Valid approaches to classifying cases and exacerbations in the general population are needed to facilitate prevention research.To assess the feasibility, reproducibility, and performance of a protocol to identify CLRD cases and exacerbations triggering emergency department (ED) visits or hospitalizations in cohorts of patients derived from general populations of adults.A protocol was developed to classify CLRD cases and severe exacerbations on the basis of review of medical records. ED and inpatient medical records were ascertained prospectively in the Hispanic Community Health Study/Study of Latinos, and inpatient records were retrospectively identified by administrative codes in the Multi-Ethnic Study of Atherosclerosis. "Probable" exacerbations were defined as a physician's diagnosis of CLRD with acute respiratory symptoms. "Highly probable" exacerbations additionally required systemic corticosteroid therapy, and "definite" exacerbations required airflow limitation or evidence of CLRD on imaging studies. Adjudicated results were compared with CLRD cases identified by spirometry and self-report, and with an administrative definition of exacerbations.Protocol-based classification was completed independently by two physicians for 216 medical records (56 ED visits and 61 hospitalizations in the Hispanic Community Health Study/Study of Latinos; 99 hospitalizations in the Multi-Ethnic Study of Atherosclerosis). Reviewer disagreement occurred in 2-5% of cases and 4-8% of exacerbations. Eighty-nine percent of records were confirmed as at least probable CLRD cases. Fifty-six percent of confirmed CLRD cases had airflow limitation on the basis of baseline study spirometry. Of records that described CLRD as the primary discharge diagnosis code, an acute exacerbation was confirmed as at least probable for 96% and as highly probable or definite for 77%. Only 50% of records with CLRD as a secondary code were confirmed, although such records accounted for over half of all confirmed exacerbations.CLRD cases and severe exacerbations without preceding documentation of airflow limitation are identified frequently in population-based cohorts of persons. A primary discharge diagnosis of CLRD is specific but insensitive for defining exacerbations. Protocol-based classification of medical records may be appropriate to supplement and to validate identification of CLRD cases and exacerbations in general population studies. Clinical trials registered with www.clinicaltrials.gov (NCT00005487 and NCT02060344).

Pulmonary function testing is often considered the basis for diagnosis in many categories of pulmonary disease. Although most of the testing methodologies are well established and widely employed, there are still many questions regarding how tests should be performed, how to ensure that reliable data are produced, what reference values and rules should be used, and how pulmonary function tests (PFTs) should be interpreted to best support clinical decision making. This conference was organized around a set of questions aimed at many of these issues. Each presenter was asked to address a specific topic regarding what tests should be done, how those test should be performed to answer a particular clinical question, and to relate test results to an accurate diagnosis and appropriate treatment of the patient. These topics included testing of adults and children, with concentration on important disease entities such as COPD, asthma, and unexplained dyspnea. Special emphasis was given to discussing reference values, lower limits of normal, interpretive strategies to optimize disease classification, and those factors directly affecting data quality. Established techniques for spirometry, lung volumes, diffusing capacity, exercise testing, and bronchial challenges were compared and contrasted with new technologies, and with technologies that might be part of pulmonary function laboratories in the near future.

Background Among older persons, the association between frailty and spirometry-confirmed respiratory impairment has not been evaluated yet. Methods By using data on white participants aged 65 to 80 years (Cardiovascular Health Study, N=3578), we evaluated cross-sectional and longitudinal associations between frailty and respiratory impairment, including their combined effect on mortality. Baseline assessments included frailty status (Fried phenotype: non-frail, pre-frail, and frail) and spirometry. Outcomes included development of frailty features (pre-frail or frail) at year 3 and respiratory impairment (airflow limitation or restrictive pattern) at year 4, and death (median follow-up, 13.2 years). Results At baseline, 48.3% of participants were pre-frail, 5.8% of participants were frail, 13.8% of participants had airflow limitation, and 9.3% of participants had restrictive pattern; 46.1% of participants subsequently died. At baseline, pre-frail and frail were cross-sectionally associated with airflow limitation (adjusted odds ratio [OR], 1.62; 95% confidence interval [CI], 1.29-2.04 and adjusted OR 1.88; 95% CI, 1.15-3.09) and restrictive pattern (adjusted OR, 1.80; 95% CI, 1.37-2.36 and adjusted OR, 3.05; 95% CI, 1.91-4.88), respectively. Longitudinally, participants with baseline frailty features had an increased likelihood of developing respiratory impairment (adjusted OR, 1.42; 95% CI, 1.11-1.82). Conversely, participants with baseline respiratory impairment had an increased likelihood of developing frailty features (adjusted OR, 1.58; 95% CI, 1.17-2.13). Mortality was highest among participants who were frail and had respiratory impairment (adjusted hazard ratio, 3.91; 95% CI, 2.93-5.22), compared with those who were non-frail and had no respiratory impairment. Conclusion Frailty and respiratory impairment are strongly associated with one another and substantially increase the risk of death when both are present. Establishing these associations may inform interventions designed to reverse or prevent the progression of either condition and to reduce adverse outcomes.

Professional societies have encouraged primary care providers to conduct spirometry testing for the detection of chronic obstructive pulmonary disease (COPD). In spite of this effort, the success rate is unacceptably low. Simple flow-sensing spirometers have technical flaws that can cause misreadings, and they are rarely checked for accuracy. When spirometry is performed by an experienced technologist, and when payment is made on the criterion of quality, the success rate for adults and school-aged children can be as high as 90%. But testing remains a challenge for younger children and the elderly. Regular feedback for the technologist about their testing results is essential. Even with an accurate spirometer, an able patient, and a skilled technologist, the ordering physician may wrongly interpret the data. Use of spirometry in primary care will continue to be problematic unless high quality testing is tied to reimbursement. Using FEV(1) or peak flow measurements to rule out airway abnormality in the majority of patients, followed by referral for more sophisticated studies in those remaining, may be the best approach. Respiratory therapists should engage in this effort.

All pulmonologists, including those recently completing training, should be competent in critically evaluating and interpreting pulmonary function tests (PFTs). In addition, some authorities recommend that respiratory therapists learn to provide preliminary PFT interpretations for the medical directors of PFT labs. The 2005 American Thoracic Society/European Respiratory Society guidelines for interpreting PFTs lack recommendations for the best reference equations for lung volumes and diffusing capacity of the lung for carbon monoxide (D(LCO)), and lack reference equations for non-whites. The pre-test probability of lung disease should be determined using a short questionnaire. The "nonspecific pattern" occurs in about 15% of patients referred to a PFT lab, but it has many clinical correlates and the course is usually benign. Less common PFT patterns and those resulting from comorbid conditions (such as obesity, respiratory muscle weakness, or heart failure) are not discussed by the guidelines. More than half of patients with interstitial lung disease have a normal ratio of D(LCO)/V(A) (alveolar volume), and many have a normal total lung capacity.

Asthma in the elderly is underdiagnosed and undertreated, and there is a paucity of knowledge on the subject. The National Institute on Aging convened this workshop to identify what is known and what gaps in knowledge remain and suggest research directions needed to improve the understanding and care of asthma in the elderly. Asthma presenting at an advanced age often has similar clinical and physiologic consequences as seen with younger patients, but comorbid illnesses and the psychosocial effects of aging might affect the diagnosis, clinical presentation, and care of asthma in this population. At least 2 phenotypes exist among elderly patients with asthma; those with longstanding asthma have more severe airflow limitation and less complete reversibility than those with late-onset asthma. Many challenges exist in the recognition and treatment of asthma in the elderly. Furthermore, the pathophysiologic mechanisms of asthma in the elderly are likely to be different from those seen in young asthmatic patients, and these differences might influence the clinical course and outcomes of asthma in this population.

Differences in COPD classification have been shown in population data sets when using fifth percentiles as the lower limit of normal (LLN) vs the current GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines of FEV(1)/FVC0.70 for detecting airway obstruction and an FEV(1) of 80% predicted for detecting and classifying the severity of COPD (GOLD/PP). Many lung function laboratories use 80% predicted to determine whether results are abnormal. Misclassification of the full range of lung diseases in large patient groups when using GOLD/PP criteria instead of the LLN has not been explored previously.We determined the discrepancy rates in pulmonary function test interpretation between the GOLD/PP and LLN methods on prebronchodilator lung function results from a large number of adult patients from the United Kingdom, New Zealand, and the United States.In 11,413 patients, the GOLD/PP method misclassified 24%. Ten percent of patients who had normal lung function were falsely classified with a disease category, and 7% of patients were falsely attributed with emphysema. The GOLD/PP method gave false-positive classifications for airflow obstruction and restrictive defects to significantly more men (P.01) and older patients (P.0001) and also missed airflow obstruction and restrictive defects in younger patients (P.0001).Using lung function tests on their own with 80% predicted and fixed cut points to determine whether a test is abnormal could misdiagnose20% of patients referred for pulmonary function tests. The GOLD/PP method introduces clinically important biases in assessing disease status that could affect allocation to treatment groups. This misclassification is avoided by using the LLN based on the fifth-percentile values.

Objective: To evaluate methods for determining excessive short-term decline in forced expiratory volume in one second (FEV 1 ) in diacetyl-exposed workers. Methods: We evaluated five methods of determining excessive longitudinal FEV 1 decline in diacetyl-exposed workers and workers from a comparative cohort: American Thoracic Society (ATS), ACOEM an 8% limit, and a relative and absolute longitudinal limit on the basis of spirometry data variability. Relative risk and incidence of excess decline were evaluated. Results: Incidence of excessive FEV 1 decline was 1% in the comparative cohort using ATS and ACOEM criteria, 4.1% using relative limit of longitudinal decline, 4.4% with absolute longitudinal limit of decline, and 5.6% by using the 8% limit. Relative risk of abnormal FEV 1 decline in diacetyl-exposed workers was elevated in all evaluated methods. Conclusion: Alternative methods for respiratory surveillance in diacetyl-exposed workers may be preferable to ATS or ACOEM.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality. Periodic spirometry is often recommended for individuals with potential occupational exposure to respiratory hazards and in medical treatment of respiratory disease, to prevent COPD or improve treatment outcome. To achieve the full potential of spirometry monitoring in preserving lung function, it is important to maintain acceptable precision of the longitudinal measurements, apply interpretive strategies that identify individuals with abnormal test results or excessive loss of lung function in a timely manner, and use the results for intervention on respiratory disease prevention or treatment modification. We describe novel, easy-to-use visual and analytical software, Spirometry Longitudinal Data Analysis software (SPIROLA), designed to assist healthcare providers in the above aspects of spirometry monitoring. Software application in ongoing workplace spirometry-based medical monitoring programs helped to identify increased spirometry data variability due to deteriorating test quality and subsequent improvement following interventions, and helped to enhance identification of individuals with excessive decline in lung function.

Sarcoidosis is a systemic granulomatous disease with predominant manifestation in the lungs, often presenting as interstitial lung disease. Pulmonary function abnormalities in sarcoidosis include restriction of lung volumes, reduction in diffusing capacity of the lung for carbon monoxide ( D L,CO ), reduced static lung compliance ( C L,s ) and airway obstruction. The aim of the present study was to assess various lung function indices, including C L,s and D L,CO , as markers of functional abnormality in sarcoidosis patients. Results from 830 consecutive patients referred for lung function tests with a diagnosis of sarcoidosis (223 in stage I, 486 in stage II and 121 in stage III) were retreospectively analysed. The mean±sd age of the patients was 40±11 yrs; 18% were active smokers and 24% were former smokers. Normal total lung capacity was found in 772 (93%) patients. Of these cases, 24.5% had a low C L,s and 21.5% had a low D L,CO . At least one abnormality was observed in 39.3% of these patients, whereas, in restrictive patients, this figure was 88%. Airway obstruction was present in 11.7% of cases. Lung volumes usually remain within the normal range and measurement of either C L,s or D L,CO often reveal impaired lung function in sarcoidosis patients, even when their lung volumes are still in the normal range; these two measurements provide complementary information.

Spirometry is the most important tool in diagnosing pulmonary disease and is the most frequently performed pulmonary function test. Since respiratory disease is the single greatest cause for morbidity and mortality on the Navajo Nation, the purpose of this study was to create new age and race-specific pulmonary nomograms for Navajo children. Five hundred fifty-eight healthy children, ages 6–14 years, attending Navajo Nation elementary schools in Arizona, were asked to perform spirometry to develop population-specific and tribe-specific nomograms for forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), and FEV1 Ratio (FEV1/FVC). Spirometry tests from 284 girls and 274 boys met American Thoracic Society quality control standards. Lung function values, except for FEV1/FVC, all increased with height. The lower limit of the normal range for FEV1/FVC was 80%. The spirometry reference equations from the healthy boys and girls were developed. Height and the natural log of height were significant predictors of FEV1, FVC, and FEF25–75% in the gender-specific models. The resulting population-specific spirometry reference equations should be used when testing Navajo children ages 6–14 years. However, the use of the NHANES III spirometry reference equations for Caucasian children may not result in significant misclassification in clinical settings providing that a maximal effort is given by the Navajo child being tested. Pediatr Pulmonol. 2009; 44:489–496. © 2009 Wiley-Liss, Inc.

Background Multiple studies have demonstrated an initial high prevalence of spirometric abnormalities following World Trade Center (WTC) disaster exposure. We assessed prevalence of spirometric abnormalities and changes in spirometry between baseline and first follow-up evaluation in participants in the WTC Worker and Volunteer Medical Monitoring Program. We also determined the predictors of spirometric change between the two examinations. Methods Prebronchodilator and postbronchodilator spirometry, demographics, occupational history, smoking status, and respiratory symptoms and exposure onset were obtained at both examinations (about 3 years apart). Results At the second examination, 24.1% of individuals had abnormal spirometry findings. The predominant defect was a low FVC without obstruction (16.1%). Between examinations, the majority of individuals did not have a greater-than-expected decline in lung function. The mean declines in prebronchodilator FEV 1 and FVC were 13 mL/yr and 2 mL/yr, respectively (postbronchodilator results were similar and not reported). Significant predictors of greater average decline between examinations were bronchodilator responsiveness at examination 1 and weight gain. Conclusions Elevated rates of spirometric abnormalities were present at both examinations, with reduced FVC most common. Although the majority had a normal decline in lung function, initial bronchodilator response and weight gain were significantly associated with greater-than-normal lung function declines. Due to the presence of spirometric abnormalities > 5 years after the disaster in many exposed individuals, longer-term monitoring of WTC responders is essential.

INSOMNIA IS THE MOST COMMON SLEEP COMPLAINT IN THE UNITED STATES, AND IS ESTIMATED TO AFFECT 10% TO 30% OF AMERICANS. Insomnia is associated with reduced quality of life and may precede depression1,2 but has not clearly been shown to be causally associated with adverse outcomes. In fact, Kripke and colleagues found a reduced mortality rate for those individuals complaining of sleeping difficulty in a 6-year follow-up study.3 Efforts to establish the prevalence, potential consequences and efficacy of treatment of insomnia have been complicated by the subjective nature and variety of its symptoms. There are several characterizations of insomnia in the literature. In addition, the DSM-III-R4 and DSM-IV5 classifications, the Research Diagnostic Criteria for Insomnia Disorder,6 and the International Classification of Sleep Disorders7 include varying criteria for making the diagnosis of insomnia. A recent National Institutes of Health (NIH) Consensus Conference on insomnia concluded, “Insomnia has historically been defined by complaints of disturbed sleep in the presence of adequate opportunity and circumstance for sleep. The disturbance may consist of one or more of three features: (1) difficulty in initiating sleep; (2) difficulty in maintaining sleep; or (3) waking up too early. A fourth characteristic, nonrestorative or poor-quality sleep, has frequently been included in the definition, although there is controversy as to whether individuals with this complaint share similar pathophysiologic mechanisms with the others.”8 The symptom of nonrestorative sleep, as noted by the NIH consensus conference, is particularly nonspecific and prevalent, and is strongly linked to depression.9 The definition used to define insomnia affects its impact; in one study, some definitions of insomnia predicted incident hypertension but others did not.10 While insomnia has not been causally associated with mortality over 6- or 7-year periods,3,11 longitudinal studies of this duration may not be long enough to demonstrate such effects, if they exist. It is possible that investigation of “upstream” events such as hypertension or other prevalent cardiovascular conditions could yield important information about the natural history of insomnia. Indeed, difficulty falling asleep was associated with an increased risk of angina in a cross-sectional study.12 In summary, the relationship between sleep complaints, medical illness, mood disorders, and hypertension is complex, and more work is needed in this area. The NIH has urged specific research efforts to “Apply well-defined diagnostic criteria to assess the prevalence, incidence, and natural history of insomnia and sleep complaints” and to “Assess the effects of insomnia on public health burdens such as premature death and health care costs.”8 An intriguing relationship exists between sleep duration and hypertension. Gangswisch13 demonstrated that short sleep duration predicted hypertension in an 8-year longitudinal analysis of the National Health and Nutrition Examination Survey. In addition, Lauderdale14 found that African Americans (AA) had shorter objectively measured sleep durations than did Caucasians in the Coronary Artery Risk Development in Young Adults study. This association between short sleep duration and hypertension could be one of the mechanisms accounting for the increased prevalence of hypertension and African Americans. The aim of this analysis was to assess the effect of specific components of insomnia on incident hypertension in the Cardiovascular Health Study. We hypothesized that insomnia complaints predict incident hypertension. As hypertension in older adults has been shown to be a risk factor for stroke, heart failure, and death, identifying easily assessable predisposing risk factors remains important. We were particularly interested in relationships between sleep complaints and hypertension in African Americans, since little data is available about this group, and the CHS cohort is enriched with African Americans. Excess cardiovascular morbidity among African Americans likely has many causes, but we hypothesized that sleep complaints could be among the factors contributing to this phenomenon.

Summary Spirometry programs (outside of primary care settings) designed to detect COPD in the general adult population are not justified, since the true positive yield (airway obstruction with an FEV(1) below 60% predicted) is very low, and the false positive rate is very high. However, spirometry is greatly under-utilised by GPs who often prescribe inhalers for patients haphazardly. Inhalers for COPD are expensive and risk serious side-effects, so they should not be prescribed for current or former smokers without confirming severe airway obstruction. A large program in Finland has shown that some GPs can perform good quality spirometry. If good quality spirometry is not available in the GP's office, patients should be referred to a local resource for pre- and post-bronchodilator spirometry. More studies are needed to show that GPs use spirometry results systematically to make decisions which truly benefit their patients with asthma or COPD.

OBJECTIVES: To evaluate the risk of incident physical disability and the decline in gait speed over a 6-year follow-up associated with a low ankle-arm index (AAI) in older adults. DESIGN: Observational cohort study. SETTING: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania. PARTICIPANTS: Four thousand seven hundred five older adults, 58% women and 17.6% black, participating in the Cardiovascular Health Study. MEASUREMENTS: AAI was measured in 1992/93 (baseline). Self-reported mobility, activity of daily living (ADL), and instrumental activity of daily living (IADL) disability and gait speed were recorded at baseline and at 1-year intervals over 6 years of follow-up. Mobility disability was defined as any difficulty walking half a mile and ADL and IADL disability was defined as any difficulty with 11 specific ADL and IADL tasks. Individuals with mobility, ADL, or IADL disability at baseline were excluded from the respective incident disability analyses. RESULTS: Lower baseline AAI values were associated with increased risk of mobility disability and ADL/IADL disability. Clinical cardiovascular disease (CVD), diabetes mellitus, and interim CVD events partially explained these associations for mobility disability and clinical CVD and diabetes mellitus partially explained these associations for ADL and IADL disability. Individuals with an AAI less than 0.9 had on average a mean decrease in gait speed of 0.02 m/s per year, or a decline of 0.12 m/s over the 6-year follow-up. Prevalent CVD partly explained this decrease but interim CVD events did not further attenuate it. CONCLUSION: Low AAI serves as marker of future disability risk. Reduction of disability risk in patients with a low AAI should consider cardiovascular comorbidity and the prevention of additional disabling CVD events.

Background Spirometry is recommended for diagnosis and management of obstructive lung disease. While many patients with asthma and COPD are cared for by primary care practices, limited data are available on the use and results associated with spirometry in primary care. Object To assess the technical adequacy, accuracy of interpretation, and impact of office spirometry. Design A before-and-after quasiexperimental design. Setting Three hundred eighty-two patients from 12 family medicine practices across the United States. Participants Patients with asthma and COPD, and staff from the 12 practices. Measurements Technical adequacy of spirometry results, concordance between family physician and pulmonary expert interpretations of spirometry test results, and changes in asthma and COPD management following spirometry testing. Results Of the 368 tests completed over the 6 months, 71% were technically adequate for interpretation. Family physician and pulmonary expert interpretations were concordant in 76% of completed tests. Spirometry was followed by changes in management in 48% of subjects with completed tests, including 107 medication changes (>85% concordant with guideline recommendations) and 102 nonpharmacologic changes. Concordance between family physician and expert interpretations of spirometry results was higher in those patients with asthma compared to those with COPD. Discussion and conclusions US family physicians can perform and interpret spirometry for asthma and COPD patients at rates comparable to those published in the literature for international primary care studies, and the spirometry results modify care.

Background Despite growing recognition that asthma is an important cause of morbidity among American Indians, there has been no systematic study of this disease in older adults who are likely to be at high risk of complications related to asthma. Characterization of the impact of asthma among American Indian adults is necessary in order to design appropriate clinical and preventive measures. Methods A sample of participants in the third examination of the Strong Heart Study, a multicenter, population-based, prospective study of cardiovascular disease in American Indians, completed a standardized respiratory questionnaire, performed spirometry, and underwent allergen skin testing. Participants were ≥ 50 years old. Results Of 3,197 participants in the third examination, 6.3% had physician-diagnosed asthma and 4.3% had probable asthma. Women had a higher prevalence of physician-diagnosed asthma than men (8.2% vs 3.2%). Of the 435 participants reported in the asthma substudy, morbidity related to asthma was high: among those with physician-diagnosed asthma: 97% reported trouble breathing and 52% had severe persistent disease. The mean FEV1 in those with physician-diagnosed asthma was 61.3% of predicted, and 67.2% reported a history of emergency department visits and/or hospitalizations in the last year, yet only 3% were receiving regular inhaled corticosteroids. Conclusions The prevalence of asthma among older American Indians residing in three separate geographic areas of the United States was similar to rates in other ethnic groups. Asthma was associated with low lung function, significant morbidity and health-care utilization, yet medications for pulmonary disease were underutilized by this population.

Definitions et subdivisions du volume pulmonaire 17S48 Preparation du patient 17S49 Determination des subdivisions pulmonaires ........ 17S49 Mesure de la CRF par plethysmographie corporelle 17S50 Introduction et theorie 17S50 Materiel 17S50 Technique de mesure 17S50 Controle qualite 17S51 Calculs 17S52 Mesure de la CRF par rincage de l’azote 17S52 Introduction et theorie 17S52 Materiel 17S52 Technique de mesure 17S53 Controle qualite 17S53 Calculs 17S54 Mesure de la Crf par dilution de l’helium 17S54 Introduction et theorie 17S54 Materiel 17S54 Technique de mesure 17S55 Controle qualite 17S56 Calculs 17S56 Mesure des volumes pulmonaires par des techniques d’imagerie 17S56 Radiographies conventionnelles 17S57 Tomodensitometrie 17S57 Imagerie par resonance magnetique 17S57 Controverses et questions critiques 17S57 Valeurs de reference 17S58 Prevention des infections 17S58 Abreviations 17S58

Udgivelsesdato: 2007-Mar

Objective:To determine the ability of patients seen for acute asthma exacerbations in the emergency department (ED) to perform good-quality FEV1measurements. Methods:Investigators from 20 EDs were trained to perform spirometry testing as part of a clinical trial that included standardized equipment with special software-directed prompts. Spirometry was done on ED arrival and 30 min, 1 h, 2 h, and 4 h later, and during follow-up outpatient visits. Measurements:Study performance criteria differed from American Thoracic Society (ATS) guidelines because of the population acuity and severity of illness as follows: ability to obtain acceptable FEV1measures (defined as two or more efforts with forced expiratory times ≥ 2 s and time to peak flow < 120 ms or back-extrapolated volume < 5% of the FVC) and reproducibility criteria (two highest acceptable FEV1values within 10% of each other). Results:Of the 620 patients (age range, 12 to 65 years), > 90% met study acceptability criteria on ED arrival and 74% met study reproducibility criteria. Mean initial FEV1was 38% of predicted. Spirometry quality improved over time; by 1 h, 90% of patients met study acceptability and reproducibility criteria. Patients with severe airway obstruction (FEV1< 25% of predicted) were initially less likely to meet quality goals, but this improved with time. The site was also an independent predictor of quality. Conclusion:When staff are well trained and prompt feedback regarding adequacy of efforts is given, modified ATS performance goals for FEV1tests can be met from most acutely ill adolescent and adult asthmatics, even within the first hour of evaluation and treatment for an asthma exacerbation.

Background Emphysema on CT is a risk factor for all-cause mortality in persons with and without airflow obstruction; however, causes of death associated with emphysema remain uncertain, particularly in the general population. Aims To test associations between quantitatively assessed emphysema on CT and cause of death in persons with and without a substantial smoking history. Methods The Multi-Ethnic Study of Atherosclerosis recruited 6814 participants, aged 45–84 years and without clinical cardiovascular disease, in 2000–2002. Per cent emphysema was defined on cardiac CT as per cent of lung voxels less than −950 Hounsfield units; emphysema on CT was defined as per cent emphysema above the upper limit of normal. Cause of death was classified by administrative codes. Proportional-hazards models were adjusted for age, race/ethnicity, gender, body mass index, smoking status, pack-years, coronary artery calcium, site and education. Additional adjustment for lung function was made in a subset with spirometry from 2004 to 2006. Results There were 1091 deaths over 12 years median follow-up. Emphysema on CT was strongly associated with increased mortality due to respiratory diseases (adjusted HR 2.94, 95% CI 1.68 to 5.15), particularly chronic lower respiratory diseases (adjusted HR 9.54, 95% CI 4.70 to 19.35), and lung cancer (adjusted HR 1.84, 95% CI 1.09 to 3.12), but not cardiovascular disease. Associations persisted among participants with fewer than 10 pack-years and those without physician-diagnosed respiratory disease, and were similar after adjustment for airflow measures and in persons without airflow limitation. Conclusions Quantitatively assessed emphysema on CT is associated with greater respiratory disease and lung cancer mortality, even among persons without traditional risk factors.

Respiratory problems are common among wildland firefighters. However, there are few studies directly linking occupational exposures to respiratory effects in this population. Our objective was to characterize wildland fire fighting occupational exposures and assess their associations with cross-shift changes in lung function. We studied 17 members of the Alpine Interagency Hotshot Crew with environmental sampling and pulmonary function testing during a large wildfire. We characterized particles by examining size distribution and mass concentration, and conducting elemental and morphological analyses. We examined associations between cross-shift lung function change and various analytes, including levoglucosan, an indicator of wood smoke from burning biomass. The levoglucosan component of the wildfire aerosol showed a predominantly bimodal size distribution: a coarse particle mode with a mass median aerodynamic diameter about 12 μm and a fine particle mode with a mass median aerodynamic diameter < 0.5 μm. Levoglucosan was found mainly in the respirable fraction and its concentration was higher for fire line construction operations than for mop-up operations. Larger cross-shift declines in forced expiratory volume in one second were associated with exposure to higher concentrations of respirable levoglucosan (p < 0.05). Paired analyses of real-time personal air sampling measurements indicated that higher carbon monoxide (CO) concentrations were correlated with higher particulate concentrations when examined by mean values, but not by individual data points. However, low CO concentrations did not provide reliable assurance of concomitantly low particulate concentrations. We conclude that inhalation of fine smoke particles is associated with acute lung function decline in some wildland firefighters. Based on short-term findings, it appears important to address possible long-term respiratory health issues for wildland firefighters. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resources: a file containing additional information on historical studies of wildland fire exposures, a file containing the daily-exposure-severity questionnaire completed by wildland firefighter participants at the end of each day, and a file containing additional details of the investigation of correlations between carbon monoxide concentrations and other measured exposure factors in the current study.]

The prevalence of asthma has increased dramatically over the last 25 years in the United States and in other nations as a result of ill-defined changes in living conditions in modern society. On 18 and 19 October 2004 the U.S. Environmental Protection Agency and the National Institute of Environmental Health Sciences sponsored the workshop “Environmental Influences on the Induction and Incidence of Asthma” to review current scientific evidence with respect to factors that may contribute to the induction of asthma. Participants addressed two broad questions: a) What does the science suggest that regulatory and public health agencies could do now to reduce the incidence of asthma? and b) What research is needed to improve our understanding of the factors that contribute to the induction of asthma and our ability to manage this problem? In this article (one of four articles resulting from the workshop), we briefly characterize asthma and its public health and economic impacts, and intervention strategies that have been successfully used to prevent induction of asthma in the workplace. We conclude with the findings of seven working groups that focus on ambient air, indoor pollutants (biologics), occupational exposures, early life stages, older adults, intrinsic susceptibility, and lifestyle. These groups found strong scientific support for public health efforts to limit in utero and postnatal exposure to cigarette smoke. However, with respect to other potential types of interventions, participants noted many scientific questions, which are summarized in this article. Research to address these questions could have a significant public health and economic impact that would be well worth the investment.

Low lung function is known to predict mortality in the general population, but the prognostic significance of emphysema on computed tomography (CT) in persons without chronic obstructive pulmonary disease (COPD) is uncertain.To determine whether greater emphysema-like lung on CT is associated with all-cause mortality among persons in the general population without airflow obstruction or COPD.Prospective cohort study.Population-based, multiethnic sample from 6 U.S. communities.2965 participants aged 45 to 84 years without airflow obstruction on spirometry.Emphysema-like lung was defined as the number of lung voxels with attenuation less than -950 Hounsfield units on cardiac CT and was adjusted for the number of total imaged lung voxels.Among 2965 participants, 50.9% of whom had never smoked, there were 186 deaths over a median of 6.2 years. Greater emphysema-like lung was independently associated with increased mortality (adjusted hazard ratio per one-half interquartile range, 1.14 [95% CI, 1.04 to 1.24]; P=0.004) after adjustment for potential confounders, including cardiovascular risk factors and FEV1. Generalized additive models supported a linear association between emphysema-like lung and mortality without evidence for a threshold. The association was of greatest magnitude among smokers, although multiplicative interaction terms did not support effect modification by smoking status.Cardiac CT scans did not include lung apices. The number of deaths was limited among subgroup analyses.Emphysema-like lung on CT was associated with all-cause mortality among persons without airflow obstruction or COPD in a general population sample, particularly among smokers. Recognition of the independent prognostic significance of emphysema on CT among patients without COPD on spirometry is warranted.National Heart, Lung, and Blood Institute.

[⇓][1] SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING” Edited by V. Brusasco, R. Crapo and G. Viegi Number 4 in this Series [1]: #F4

Severe airways obstruction and bronchiolitis obliterans have been reported in microwave popcorn production workers and attributed to inhalation of flavoring agents. We investigated whether exposure to flavoring agents is associated with airways inflammation in popcorn production workers.Fifty-nine workers with high exposures and 22 patients with low exposures to flavoring vapors completed a questionnaire, spirometry, and sputum induction. Sputum cell counts were categorized as "high" if greater than (and "low" if less than or equal to) the median cell counts of a healthy external control group (n = 24). We compared high- and low-exposure groups as well as all workers with control subjects.Neutrophil concentrations in nonsmoking workers were significantly higher than those of the healthy nonsmoking control group (p0.05). The smoking-adjusted odds ratio for high neutrophil count (1.63 x 10(5)/mL) was 3.8 (95% confidence interval, 1.3 to 11.5) in the high-exposure group compared with the low-exposure group. Sputum interleukin-8 and eosinophil cationic protein levels were higher in high-exposure workers than in low-exposure workers (p0.05). For the worker group, mean values of FEV1 percentage of predicted and FEV1/FVC percentage of predicted were95%. There were no relationships between sputum characteristics and the presence of airways obstruction.High exposure to popcorn flavoring agents is associated with neutrophilic airway inflammation in popcorn production workers. These data provide further evidence that popcorn production workers face a significant occupational hazard through exposure to flavoring agents.