Restrictive pulmonary dysfunction at spirometry and mortality in the elderly

OBJECTIVES: To evaluate the association between pulmonary restriction and mortality in the elderly, taking into account potential confounders not considered in the past (disability, cognitive dysfunction, diabetes, and visceral obesity). DESIGN: Longitudinal study. SETTING: Community-based. PARTICIPANTS: Twelve hundred sixty-five patients (51.9% men) aged 65-97 years old from the Salute Respiratoria nell'Anziano (SaRA) Italian multicentric study. MEASUREMENTS: Participants were divided in 4 groups: normal spirometry (NS): FEV1/FVC>/=70%, FVC>/=80% of predicted; restrictive ventilatory pattern (RVP): FEV1/FVC>/=70%, FVC<80%; obstructive ventilatory pattern (OVP): FEV1/FVC<70%, FVC>/=80%, and mixed ventilatory pattern (MVP): FEV1/FVC<70%, FVC<80%. We calculated the association between restriction and mortality corrected for potential confounders using a multivariable Cox regression model. RESULTS: We found a prevalence of RVP, OVP and MVP of 10.9%, 25.4%, and 17.3%, respectively. Compared to people with normal spirometric pattern, disability (19.6% vs. 10.1%), poor physical performance (35.4% vs. 22.3%), cognitive impairment (21.0% vs. 11.5%), increased waist circumference (62.1% and 26.8%), and kyphoscoliosis (56.8 and 13.5%) were more prevalent in the RVP group. After correction for potential confounders, RVP was associated with increased mortality (HR: 1.89; 95% CI: 1.15-3.11), as well as OVP (HR: 2.33; 95% CI: 1.58-3.11) and MVP (HR: 2.60; 95% CI: 1.74-3.93). Other factors associated with mortality were disability (HR: 1.92; 95% CI: 1.35-2.72), poor physical performance (HR: 1.37; 95% CI: 1.01-1.85), cognitive impairment (HR: 1.55; 95% CI: 1.06-2.27), depression (HR: 1.57; 95% CI: 1.16-2.13) and diagnosis of stroke (HR: 1.90; 95% CI: 1.18-3.05). CONCLUSIONS: RVP is associated with higher mortality in the elderly and, thus, deserves the same attention paid to an obstructive pattern. However, mechanisms mediating this association need to be clarified.     

Obstructive and restrictive lung disease and functional limitation: data from the Third National Health and Nutrition Examination

OBJECTIVE: To determine functional limitations in adults with obstructive or restrictive lung disease or respiratory symptoms. DESIGN: Cross-sectional study. SUBJECTS: Adult participants in phase 2 of the Third National Health and Nutrition Examination Survey, 1991-94. METHODS: We classified subjects using spirometric criteria into the following mutually exclusive categories using the forced expiratory volume in 1 s (FEV1), the forced vital capacity (FVC), the FEV1/FVC ratio and the presence of respiratory symptoms: severe obstruction, moderate obstruction, mild obstruction, respiratory symptoms only, restrictive lung disease and no lung disease. We developed regression models to predict functional limitations (unable to walk a quarter of a mile, unable to lift 10 pounds, needs help with daily activities) that controlled for age, race, sex, education, smoking status, body mass index and comorbid conditions. RESULTS: Severe and moderate obstruction were associated with an increased risk of being unable to walk a quarter of a mile [odds ratio (OR) 8.4, 95% confidence interval (CI) 3.6, 19.9 and OR 2.4, 95% CI 1.4, 4.0]. Restrictive lung disease and the presence of respiratory symptoms in the absence of lung function impairment were also associated with an increased risk of this outcome (OR 2.8, 95% CI 1.4, 5.6 and OR 2.8, 95% CI 2.0, 3.9). Similar results were obtained for the outcomes of being unable to lift 10 pounds or needing help with daily activities. CONCLUSIONS: The presence of obstructive or restrictive lung disease, or respiratory symptoms in the absence of lung function impairment is associated with increased functional impairment.     

Association between Sarcopenia and Metabolic Syndrome in Chronic Obstructive Pulmonary Disease: The Korea National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2011

Aim: It is not clear whether the restrictive or obstructive pattern of spirometry is associated with metabolic syndrome. We investigated the associations between restrictive and obstructive spirometric patterns and metabolic risk factors using data from the Korea National Health and Nutrition Examination Survey (KNHANES). Additionally, we investigated whether sarcopenia is associated with metabolic syndrome in patients with chronic obstructive pulmonary disease (COPD). Methods: Using data from KNHANES between 2008 and 2011, we enrolled 8,145 subjects (normal lung function: 6,077, obstructive spirometric pattern: 1,039, restrictive pattern: 1,029) aged ≥40 years who underwent anthropometric measurement, laboratory tests, spirometry and estimation of appendicular muscle mass. Sarcopenia was defined as an appendicular skeletal muscle mass divided by body weight squared <2 SD below the sex-specific mean for the young reference group. Results: Sarcopenia was found in 32.8% of male and 12.2% of female patients with COPD. The odds ratio (OR) of metabolic syndrome for the restrictive spirometric pattern in male was 1.29 (95% confidence interval [CI], 1.02–1.65), and that for obstructive pattern in males was 0.99 (95% CI, 0.79–1.26) after adjustments for covariables (female restrictive pattern (ORs, 1,45; 95% CI, 1.09–1.91) and female obstructive pattern (ORs 0.73; 95% CI, 0.49–1.09). After adjustment for other confounding factors, the risk of metabolic syndrome was higher in sarcopenic male (OR, 1.88; 95% CI, 1.27–2.77) with COPD than in those without sarcopenia. Conclusions: The restrictive spirometric pattern is associated with metabolic syndrome, and sarcopenia may contribute to the risk of metabolic syndrome in male patients with COPD.     

Spirometrically gated high-resolution CT findings in COPD: lung attenuation vs lung function and dyspnea severity

STUDY OBJECTIVES: The aim of this study was to investigate the relationship between high-resolution CT (HRCT) lung attenuation measurements, acquired under spirometric control of inspiratory and expiratory lung volume, and pulmonary dysfunction as well as dyspnea severity in patients with COPD.Patients and design: In 51 patients with COPD, we compared by linear regression, univariate and multivariate logistic regression airflow limitation (FEV(1)/vital capacity [VC]), hyperinflation (percentage of predicted residual volume [RV%]), parenchymal loss (percentage of predicted diffusing capacity of the lung for carbon monoxide [Dlco%]), and Medical Research Council (MRC) dyspnea scale with relative area with attenuation values < - 950 HU at 90% of VC [RAI(950)] and < - 910 HU at 10% of VC, respectively, and with mean lung attenuation measured at the same levels of VC (mean CT lung density at 10% of VC, and mean CT lung density at 90% of VC [MeanCTEXP]). RESULTS: All HRCT attenuation measurements were significantly related with functional abnormalities and dyspnea severity. In multivariate logistic models, with 1 indicating worse changes in dichotomous outcome variables, MeanCTEXP independently predicted FEV(1)/VC (odds ratio [OR], 0.24; 95% confidence interval [CI], 0.11 to 0.56), RV% (OR, 0.57; 95% CI, 0.42 to 0.77), and MRC dyspnea scale (OR, 0.63; 95% CI, 0.48 to 0.82), while RAI(950) independently predicted Dlco% (OR, 1.90; 95% CI, 1.37 to 2.65). CONCLUSIONS: Spirometrically gated measurements of HRCT lung attenuation reflect differently functional changes and dyspnea perception in COPD. Inspiratory measurements assess the extent of emphysematous tissue loss, and expiratory measurements may reflect airflow limitation and lung hyperinflation with attendant dyspnea perception. Pulmonary dysfunction in COPD cannot be assessed by a single modality of lung attenuation measurement.     

Obstructive and restrictive spirometric patterns: fixed cut-offs for FEV1/FEV6 and FEV6.

The purpose of this study was to determine fixed cut-off points for forced expiratory volume in one second (FEV(1))/FEV(6) and FEV(6) as an alternative for FEV(1)/forced vital capacity (FVC) and FVC in the detection of obstructive and restrictive spirometric patterns, respectively. For the study, a total of 11,676 spirometric examinations, which took place on Caucasian subjects aged between 20-80 yrs, were analysed. Receiver-operator characteristic curves were used to determine the FEV(1)/FEV(6) ratio and FEV(6) value that corresponded to the optimal combination of sensitivity and specificity, compared with the commonly used fixed cut-off term for FEV(1)/FVC and FVC. The data from the current study indicate that FEV(1)/ FEV(6) <73% and FEV(6) <82% predicted can be used as a valid alternative for the FEV(1)/FVC <70% and FVC <80% pred cut-off points for the detection of obstruction and restriction, respectively. The statistical analysis demonstrated very good, overall, agreement between the two categorisation schemes. For the spirometric diagnosis of airway obstruction (prevalence of 45.9%), FEV(1)/FEV(6) sensitivity and specificity were 94.4 and 93.3%, respectively; the positive and negative predictive values were 92.2 and 95.2%, respectively. For the spirometric detection of a restrictive pattern (prevalence of 14.9%), FEV(6) sensitivity and specificity were 95.9 and 98.6%, respectively; the positive and negative predictive values were 92.2 and 99.3%, respectively. This study demonstrates that forced expiratory volume in one second/forced expiratory volume in six seconds <73% and forced expiratory volume in six seconds <82% predicted, can be used as valid alternatives to forced expiratory volume in one second/forced vital capacity <70% and forced vital capacity <80% predicted, as fixed cut-off terms for the detection of an obstructive or restrictive spirometric pattern in adults.     

Discriminating between cardiac and pulmonary dysfunction in the general population with dyspnea by plasma pro-B-type natriuretic peptide.

OBJECTIVES: This study was designed to determine whether measurement of plasma pro-B-type natriuretic peptide (proBNP) could be used in discriminating between cardiac and pulmonary dyspnea in the general population. BACKGROUND: Natriuretic peptides are useful markers in ruling out acute cardiac dyspnea in the emergency department, but their diagnostic significance in evaluating chronic dyspnea in the general population is unknown. METHODS: Within the Copenhagen City Heart Study, a large, community-based population study, dyspnea was evaluated by spirometry, oxygen saturation, echocardiography, and plasma proBNP. RESULTS: Of 2,929 participants, 959 reported dyspnea. The plasma proBNP concentration was higher in the group with dyspnea (mean 17.8 pmol/l; 95% confidence interval [CI] 16.3 to 19.4 pmol/l) than in the group without (10.6 pmol/l; 95% CI 10.0 to 11.4 pmol/l; p < 0.001). In the group with dyspnea, left ventricular hypertrophy and/or systolic dysfunction was associated with a 2.6-fold increase in plasma proBNP concentration (p < 0.001), whereas pulmonary dysfunction was not associated with increased plasma proBNP (p = 0.66). Using multivariable regression analysis, a model to estimate the expected concentration of plasma proBNP based on age and gender was established for dyspneic subjects: an actual plasma proBNP concentration below half of the expected value ruled out left ventricular systolic and diastolic dysfunction (sensitivity 100%, 95% CI 100% to 100%; specificity 15%, 95% CI 12% to 17%). CONCLUSIONS: In the general population with dyspnea, plasma proBNP concentrations are increased in left ventricular dilatation, hypertrophy, systolic dysfunction, or diastolic dysfunction, but are unaffected by pulmonary dysfunction.     

Indications for spirometry in outpatients with respiratory disease

It has been suggested that spirometry should be incorporated into the routine examination of every patient, analogous to obtaining vital signs. To determine the impact of spirometry on the management of outpatients with respiratory disease, spirometry was performed on 150 consecutive patients (123 men and 27 women, mean age 57 +/- 12 years) seen in our pulmonary disease outpatient clinics. Patients with obstructive (n = 75), restrictive (n = 31), mixed (n = 26) or other respiratory diseases (n = 18) were initially assessed by history and physical examination and classified as improved, stable, or worse compared to previous visits. A clinical management plan (CMP) was formulated based on this initial evaluation. Spirometric results were then made available to the examiner who could then make changes in the proposed CMP. The addition of spirometric results caused alteration of the CMP in only eight (5 percent) patients; in the remaining 142 patients, results did not affect the CMP. Two clinical findings identified those patients whose CMP was most likely to be altered by spirometry: severity of lung dysfunction (determined from previous spirometry) and deterioration of clinical status (judged by history and physical examination). Of the eight patients whose CMP was changed after review of spirometry, six (75 percent) had previous severe ventilatory dysfunction (FEV1 or FVC less than or equal to 40 percent of predicted or FEV1/FVC ratio less than or equal to 0.40). In 6 of 38 patients (16 percent) with severe ventilatory dysfunction, CMP was altered after spirometry while only 2 of 112 patients (1.8 percent) with mild or moderate dysfunction had changes in their CMP. Patients who were clinically assessed as worse compared to their previous visit were more likely to have their CMP altered after review of spirometry when compared to those considered improved or stable by a ratio of 6:1. These results suggest that spirometry is most likely to supplement the physician's history and physical examination in the management of outpatients with pulmonary disease when the initial evaluation suggests that the patient has clinically deteriorated since the previous clinic visit, or when he or she has previous severe ventilatory dysfunction.     

Response to one-legged cycling in patients with COPD

BACKGROUND: In patients with COPD, exercise intensity is often limited by the ventilatory system. We hypothesized that by exercising with a smaller muscle mass, ventilatory-limited patients would perform more high-intensity, muscle-specific work. The study objectives were as follows: (1) to determine the limitations of exercising with a smaller muscle mass, compared with conventional two-legged exercise; and (2) to determine the endurance time, using the same muscle-specific intensity, during one-legged vs two-legged exercise. METHODS: Nine patients (mean +/- SD FEV1, 36 +/- 13% of predicted) completed incremental exercise, and nine other patients (mean FEV1, 42 +/- 16% of predicted) completed constant-power exercise. Nine healthy subjects (FEV1, 104 +/- 14% of predicted) completed both tests. All subjects completed tests using two-legged and one-legged pedaling. RESULTS: Peak oxygen uptake (VO2peak) was similar during one-legged and two-legged incremental exercise among patients (difference, 0.03 L/min; 95% confidence interval [CI], -0.10 to 0.16 L/min; p = 0.60), as were ventilation and dyspnea scores. VO2peak was lower during one-legged vs two-legged exercise (-0.57 mL/min; 95% CI, -0.81 to -0.32 mL/min; p < 0.001) among healthy subjects with substantial ventilatory and heart rate reserve. Patients endured one-legged pedaling at a constant power longer than two-legged pedaling (16.97 min; 95% CI, 9.98 to 23.96 min; p < 0.001), resulting in greater work (12.48 kilojoules [kJ]; 95% CI, 2.58 to 22.39 kJ; p = 0.02). Healthy subjects completed similar work (-4.02 kJ; 95% CI, -18.59 to 10.55 kJ; p = 0.54) with one-legged vs two-legged pedaling. CONCLUSION: These observations demonstrate the effectiveness of using one-legged exercise at the same muscle-specific intensity in extending the duration of exercise among patients with COPD. This has important implications for training approaches designed to enhance exercise function among ventilatory-limited patients.     

The association between metabolic syndrome and restrictive ventilatory dysfunction in older persons

BACKGROUND: The restrictive, but not the obstructive respiratory dysfunction, is associated with an increased risk of developing type 2 diabetes mellitus. Our aim was to verify in an elderly nondiabetic population whether a restrictive respiratory pattern was associated with a higher prevalence of metabolic syndrome and increased insulin resistance than were obstructive and normal respiratory patterns. METHODS: We performed a cross-sectional study of 159 consecutive nondiabetic elderly persons attending two social centers. According to their spirometric pattern, volunteers were classified into the following categories: normal spirometry, obstructive (forced expiratory volume in 1 second/forced vital capacity<0.70), and restrictive pattern (forced vital capacity<80% predicted, forced expiratory volume in 1 second/forced vital capacity>or=0.70). Independent correlates of the metabolic syndrome were identified. RESULTS: The prevalence of metabolic syndrome was higher in restrictive (56%) than in both normal (21.4%, p=.001) and obstructive volunteers (12.9%, p=.001). Insulin resistance, as assessed by the log transformation of the HOmeostasis Model Assessment (HOMA), was higher in restrictive than in obstructive and normal volunteers (1+/-0.6 vs 0.3+/-0.6 and 0.5+/-0.5, p<.001). Restriction was an independent correlate of metabolic syndrome, also after adjustment for waist circumference and body mass index (odds ratio=3.23, 95% confidence interval, 1.23-8.48; p=.01). CONCLUSION: Restrictive, but not obstructive respiratory pattern, is associated with metabolic syndrome and insulin resistance, and does not only reflect a limitation of ventilation due to visceral obesity. Metabolic abnormalities likely mediate cardiovascular risk in patients with restrictive respiratory impairment.     

FEV1/FEV6 and FEV6 as an alternative for FEV1/FVC and FVC in the spirometric detection of airway obstruction and restriction

STUDY OBJECTIVES: To evaluate the use of the FEV(1)/forced expiratory volume at 6 s of exhalation (FEV(6)) ratio and FEV(6) as an alternative for FEV(1)/FVC and FVC in the detection of airway obstruction and lung restriction, respectively. SETTING: Pulmonary function laboratory of the Academic Hospital of the Free University of Brussels. PARTICIPANTS: A total of 11,676 spirometric examinations were analyzed on subjects with the following characteristics: white race; 20 to 80 years of age; 7,010 men and 4,666 women; and able to exhale for at least 6 s. METHODS: Published reference equations were used to determine lower limits of normal (LLN) for FEV(6), FVC, FEV(1)/FEV(6), and FEV(1)/FVC. We considered a subject to have obstruction if FEV(1)/FVC was below its LLN. A restrictive spirometric pattern was defined as FVC below its LLN, in the absence of obstruction. From these data, sensitivity and specificity of FEV(1)/FEV(6) and FEV(6) were calculated. RESULTS: For the spirometric diagnosis of airway obstruction, FEV(1)/FEV(6) sensitivity was 94.0% and specificity was 93.1%; the positive predictive value (PPV) and negative predictive value (NPV) were 89.8% and 96.0%, respectively. The prevalence of obstruction in the entire study population was 39.5%. For the spirometric detection of a restrictive pattern, FEV(6) sensitivity was 83.2% and specificity was 99.6%; the PPVs and NPVs were 97.4% and 96.9%, respectively. The prevalence of a restrictive pattern was 15.7%. Similar results were obtained for male and female subjects. When diagnostic interpretation differed between the two indexes, measured values were close to the LLN. CONCLUSIONS: The FEV(1)/FEV(6) ratio can be used as a valid alternative for FEV(1)/FVC in the diagnosis of airway obstruction, especially for screening purposes in high-risk populations for COPD in primary care. In addition, FEV(6) is an acceptable surrogate for FVC in the detection of a spirometric restrictive pattern. Using FEV(6) instead of FVC has the advantage that the end of a spirometric examination is more explicitly defined and is easier to achieve.     

Effects of withdrawal of inhaled steroids in men with severe irreversible airflow obstruction

Inhaled corticosteroid therapy has proven efficacy for asthmatics, but the benefit for patients with chronic obstructive pulmonary disease (COPD) is less well supported. We hypothesized that withdrawal of inhaled steroids in elderly patients with severe irreversible airway obstruction would not lead to a deterioration in respiratory function. We designed a prospective, double-blind, randomized, placebo-controlled, crossover study to follow spirometry, quality of life questionnaire, six-minute (6-min) walk test, and sputum markers of inflammation during a 6-wk placebo treatment period and a 6-wk treatment period with beclomethasone dipropionate (BDP), 336 microg/d. There were 24 men receiving BDP who entered the study; 15 completed the study. Their mean age was 66.9 +/- 1.9 yr, and mean FEV(1) was 1.61 +/- 0.1 L (47% of predicted). There was a significant decrease in the mean FEV(1 )while using the placebo inhaler (1.70 L versus 1.60 L, baseline versus placebo: 95% CI, 0.002 to 0.195; p < 0.05). There was a decrease in the mean percentage change in FEV(1) for the study subjects during the placebo treatment period as compared with the BDP treatment period (-6.28 versus 5.03%, placebo versus BDP: 95% CI, -23.38 to 0.76; p = 0.06). Six-minute walk test results and sputum analysis for cell count and differential were not significantly different during placebo and BDP treatment periods. Borg scale assessment of dyspnea after exercise was increased while using the placebo inhaler as compared with baseline, and decreased during the BDP treatment period. Chronic Respiratory Disease Questionnaire (CRQ) scores revealed no significant difference between placebo and BDP. This study has demonstrated that in elderly patients with severe irreversible airway obstruction, withdrawal of inhaled corticosteroid therapy leads to a deterioration in ventilatory function and increased exercise-induced dyspnea.     

Pulmonary function in the Marfan syndrome

To explore the causes of reported abnormalities in pulmonary function in persons with the Marfan syndrome, we analyzed retrospective anthropometric and pulmonary function tests in 79 patients. For ten subjects, there were matched, related control subjects who did not have a connective tissue disorder. Patients had lower values of FVC and TLC than the values expected for their standing heights (83 and 91 percent). However, when sitting height was used to calculate expected spirometric values, patients free of severe deformity of the thoracic cage did not have significant spirometric abnormalities (FVC 105 percent, FEV1 92 percent). However, patients with moderate-to-severe pectus excavatum or scoliosis (common features of the Marfan syndrome) had marked reductions in total lung capacity as well as in FVC and FEV1, suggesting a restrictive ventilatory defect. The abnormalities of pulmonary function often found in clinical laboratories can be explained in most cases by inappropriate use of standing height to calculate expected values, by thoracic cage deformity, or by both. We have found no evidence from standard tests of pulmonary function for a connective tissue defect of lung parenchyma that is of clinical importance in Marfan patients who lack chest wall deformity.     

Respiratory impairment and COPD hospitalisation in older persons: a competing risk analysis

The aim of the present study was to evaluate, among older persons, the association between respiratory impairment and hospitalisation for chronic obstructive pulmonary disease (COPD), based on spirometric Z-scores, i.e. the LMS (lambda, mu, sigma) method, and a competing risk approach. Using data on 3,563 white participants aged 65-80 yrs (from the Cardiovascular Health Study) we evaluated the association of LMS-defined respiratory impairment with the incident of COPD hospitalisation and the competing outcome of death without COPD hospitalisation, over a 5-yr period. Respiratory impairment included airflow limitation (mild, moderate or severe) and restrictive pattern. Over a 5-yr period, 276 (7.7%) participants had a COPD hospitalisation incident, whereas 296 (8.3%) died without COPD hospitalisation. The risk of COPD hospitalisation was elevated more than two-fold in LMS-defined mild and moderate airflow limitation and restrictive pattern (adjusted HR (95% CI): 2.25 (1.25-4.05), 2.54 (1.53- 4.22) and 2.65 (1.82-3.86), respectively), and more than eight-fold in LMS-defined severe airflow limitation (adjusted HR (95% CI) 8.33 (6.24-11.12)). Conversely, only LMS-defined restrictive-pattern was associated with the competing outcome of death without COPD hospitalisation (adjusted HR (95% CI) 1.68 (1.22-2.32)). In older white persons, LMS-defined respiratory impairment is strongly associated with an increased risk of COPD hospitalisation. These results support the LMS method as a basis for defining respiratory impairment in older persons.     

Impact of respiratory symptoms and pulmonary function on quality of life of long-term survivors of non-small cell lung cancer

PURPOSE: To describe respiratory symptoms and pulmonary function among long-term survivors of non-small cell lung cancer (NSCLC), and their relationship to quality of life (QOL). METHODS: Cross-sectional survey of disease-free, 5-year minimum survivors of NSCLC (n = 142; 54% women; average age, 71 years); the majority (74%) had received a lobectomy. Analysis included frequency of self-reported respiratory symptoms (cough, phlegm, wheezing, breathlessness) as measured by the American Thoracic Society questionnaire, pulmonary function findings from hand-held spirometry, and QOL (Short Form-36). RESULTS: Two thirds of survivors reported at least one respiratory symptom (mean, 1.3; SD, 1.2): 25% cough, 28% phlegm, 31% wheezing, and 39% dyspnea. Twenty-one percent reported that they spent most of the day in bed in the past 12 months because of respiratory symptoms. Average FEV(1) percentage predicted was 68% (SD, 23); 21% had < 50% predicted FEV(1). Based on spirometry results, 36% had a moderate/severe obstructive and/or restrictive ventilatory disorder. Survivors exposed to second-hand smoke (28%) were more than three times as likely to report respiratory symptoms. Respiratory symptom burden contributed to diminished QOL in several domains. CONCLUSIONS: The majority of these survivors experienced respiratory symptoms, and more than one third reported dyspnea, including one of five patients with seriously diminished pulmonary function. Symptom burden, rather than ventilatory impairment, contributed to diminished QOL. Further study is needed to determine the patterns and effective management of posttreatment respiratory symptoms on survivors of lung cancer.     

Airways obstruction in survivors of thoracoplasty: reversibility is greater in non-smokers

OBJECTIVE: Before the advent of antituberculous chemotherapy, thoracoplasty (TPL) was the definitive form of therapy for cavitary pulmonary tuberculosis. This study aimed to characterize the late functional sequelae of TPL, and to establish the degree of reversibility of any consequent airway obstruction. METHODOLOGY: Pulmonary function was studied in 21 long-term (mean 35 years) survivors of TPL between the years 1990-2001. RESULTS: A mixed obstructive/restrictive defect was found in this patient cohort. After inhalation of bronchodilator, marginal increases in FEV(1) and FVC and marginal decreases in FRC, RV and TLC were observed. Maximum mid-expiratory flow rate was severely reduced (28.8% of predicted), but reversibility after inhaled beta(2)-agonist was highest for this parameter of pulmonary function (mean 11%). Smokers had a higher RV (P = 0.04), suggesting hyperinflation, while non-smokers had a larger increase in FEV(1)/FVC ratio postbronchodilator (P = 0.004), suggesting more marked reversibility of airways obstruction in this group. CONCLUSIONS: Long-term survivors of TPL have an obstructive as well as a restrictive ventilatory defect. These patients have partial reversibility of the obstructive defect. The degree of reversibility found suggests that bronchodilator therapy may help these patients.     

Incidence of chronic obstructive pulmonary disease in a cohort of young adults according to the presence of chronic cough and phlegm

RATIONALE: The few prospective studies aimed at assessing the incidence of chronic obstructive pulmonary disease (COPD) in relation to the presence of chronic cough/phlegm have produced contrasting results. OBJECTIVES: To assess the incidence of COPD in a cohort of young adults and to test whether chronic cough/phlegm and dyspnea are independent predictors of COPD. METHODS: An international cohort of 5,002 subjects without asthma (ages 20-44 yr) with normal lung function (FEV(1)/FVC ratio >/= 70%) from 12 countries was followed from 1991-2002 in the frame of the European Community Respiratory Health Survey II. Incident cases of COPD were those who had an FEV(1)/FVC ratio less than 70% at the end of the follow-up, but did not report having had a doctor diagnose asthma during the follow-up. MAIN RESULTS: The incidence rate of COPD was 2.8 cases/1,000/yr (95% confidence interval [CI], 2.3-3.3). Chronic cough/phlegm was an independent and statistically significant predictor of COPD (incidence rate ratio [IRR], 1.85; 95% CI, 1.17-2.93) after adjusting for smoking habits and other potential confounders, whereas dyspnea was not associated with the disease (IRR = 0.98; 95% CI, 0.64-1.50). Subjects who reported chronic cough/phlegm both at baseline and at the follow-up had a nearly threefold-increased risk of developing COPD with respect to asymptomatic subjects (IRR = 2.88; 95% CI, 1.44-5.79). CONCLUSIONS: The incidence of COPD is substantial even in young adults. The presence of chronic cough/phlegm identifies a subgroup of subjects with a high risk of developing COPD, independently of smoking habits.     

Risk of specific congenital abnormalities in offspring of women with diabetes.

AIMS: To assess the extent to which the increased risk of congenital abnormalities seen in women with pre-gestational insulin-treated diabetes mellitus is unspecific or related to the embryology of specific organs. METHODS: Cases with congenital abnormalities were identified in the population-based Hungarian Congenital Abnormality Registry from 1980 to 1996 with two newborn children without congenital abnormality selected from the National Birth Registry as controls. We adjusted for parity, maternal age, and use of antipsychotic drugs. RESULTS: Among cases we found 63/22,843 babies with maternal diabetes compared with 50/38,151 in the control group [adjusted prevalence odds ratio (POR) 2.1; 95% CI 1.5-3.1]. The association was strongest for the following congenital abnormalities: renal agenesis (POR: 14.8; 95% CI, 3.5-62.1), obstructive congenital abnormalities of the urinary tract (POR: 4.3; 95% CI, 1.3-13.9), cardiovascular congenital abnormalities (POR: 3.4; 95% CI, 2.0-5.7), and multiple congenital abnormalities (POR: 5.0; 95% CI, 2.4-10.2). CONCLUSIONS: These data indicate that pre-gestational maternal diabetes is associated with strong teratogenic effects on the kidney, urinary tract, and heart, and strongly associated with multiple congenital abnormalities. We found no material association between diabetes and spinal congenital abnormalities and limb deficiencies.     

How accurate is spirometry at predicting restrictive pulmonary impairment?

OBJECTIVE: To determine the accuracy with which spirometric measurements of FVC and expiratory flow rates can diagnose the presence of a restrictive impairment. DESIGN: The pulmonary function tests of 1,831 consecutive white adult patients who had undergone both spirometry and lung volume measurements on the same visit over a 2-year period were analyzed. The probability of restrictive pulmonary impairment, defined as a reduced total lung capacity (TLC) below the lower limit of the 95% confidence interval, was determined for each of several categoric classifications of the spirometric data, and additionally for each of several interval levels of the FVC and the FEV1/FVC ratio. SETTING: A large clinical laboratory in a university teaching hospital using quality-assured and standardized spirometry and lung volume measurement techniques according to American Thoracic Society standards. RESULTS: Two hundred twenty-five of 1,831 patients (12.3%) had a restrictive defect. The positive predictive value of spirometry for predicting restriction was relatively low; of 470 patients with a low FVC on spirometry, only 41% had restriction confirmed on lung volume measurements. When the analysis was confined to the 264 patients with a restrictive pattern on spirometry (ie, low FVC and normal or above normal FEV1/FVC ratio), the positive predictive value was 58%. Conversely, spirometry had a very favorable negative predictive value; only 2.4% of patients (32 of 1,361) with a normal vital capacity (VC) on spirometry had a restrictive defect by TLC measurement. The probability of a restrictive defect was directly and linearly related to the degree of reduction of FVC when the FVC was < 80% of predicted (p = 6.002). Combining the FVC and the FEV1/FVC ratio improved the predictive ability of spirometry; for all values of FVC < 80% of the predicted amount, the likelihood of restrictive disease increased as the FEV1/FVC ratio increased. CONCLUSIONS: Spirometry is very useful at excluding a restrictive defect. When the VC is within the normal range, the probability of a restrictive defect is < 3%, and unless restrictive lung disease is suspected a priori, measurement of lung volumes can be avoided. However, spirometry is not able to accurately predict lung restriction; < 60% of patients with a classical spirometric restrictive pattern had pulmonary restriction confirmed on lung volume measurements. For these patients, measurement of the TLC is needed to confirm a true restrictive defect.     

Relationships of carbon dioxide retention to ventilatory impairment and hypoxemia in chronic obstructive lung disease

In a group of 80 male patients (average age 52.5 years) with severe obstructive ventilatory impairment (FEV1.0 less than 40% of predicted) due to chronic bronchitis and/or emphysema, the blood carbon dioxide tension measured at rest, in a stable clinical status, was confronted to the spirometric variables and the oxygen tension. PaCO2 (range 31--60 mm Hg) was loosely related to the VC (r = -0.28) and the FEV (r = -0.30, both p less than 0.05) and strongly related to the PaO2 (r = 0.60; p less than 0.001). When patients were classified as bronchitic or emphysematous according to clinical, roentgenologic and biological criteria, the correlations above were found to be higher for bronchitics. In patients with chronic bronchitis with severe obstruction a very good estimation of PaCO2 is possible from PaO2: PaCO2 = 75.8-0.44 PaO2 (SEE 0.4 MM Hg).     

Gender-related differences in severe, early-onset chronic obstructive pulmonary disease

Men have higher prevalence rates of chronic obstructive pulmonary disease (COPD) than women, which has been attributed to the historically higher rates of cigarette smoking in males. However, the increased rates of cigarette smoking in females within the last several decades have been associated with steadily increasing rates of COPD in women. As part of a study of the genetics of severe, early-onset COPD, we assembled a group of 84 probands with severe, early-onset COPD (without severe alpha(1)-antitrypsin deficiency) and 348 of their first-degree relatives. We found a markedly elevated prevalence (71.4%) of females among the early-onset COPD probands. Among the entire group of first-degree relatives of early-onset COPD probands, univariate analysis demonstrated similar spirometric values and bronchodilator responsiveness in males and females; however, among current or ex-smokers, female first-degree relatives had significantly lower FEV(1)/ FVC (81.4 +/- 17.2% in females versus 87.0 +/- 12.9% in males, p = 0.009) and significantly greater bronchodilator responsiveness (expressed as percentage of baseline FEV(1)) (7.7 +/- 9.4% pred in females versus 4.1 +/- 6.4% pred in males, p = 0.002). Female smoking first-degree relatives were significantly more likely to demonstrate profound reductions in FEV(1) (< 40% pred) than male smoking first-degree relatives (p = 0. 03). Multivariate analysis, performed with generalized estimating equations, demonstrated that current or ex-smoking female first-degree relatives had significantly greater risk of FEV(1) < 80% pred (OR 1.91, 95% CI 1.03- 3.54), FEV(1) < 40% pred (OR 3.56, 95% CI 1.08-11.71), and bronchodilator response greater than 10% of baseline FEV(1) (OR 4.74, 95% CI 1.91-11.75). These results suggest that women may be more susceptible to the development of severe COPD.