Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease that often causes disabling dyspnea. In IPF and other lung diseases, patient-reported outcomes (PROs)—questionnaires designed to gather information from the patient's perspective—can determine whether therapies affect dyspnea or other outcomes meaningful to patients. Before a PRO can be used confidently as an outcome measure in a longitudinal trial, studies must demonstrate the PRO's ability to capture change over time in the target population. Our goal in this study was to examine whether the UCSD Shortness of Breath Questionnaire does so in patients with IPF.
We used data from the Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis (STEP-IPF) to perform analyses that examined associations between UCSD scores and five external measures (anchors) at baseline and over time. Anchors included the Activity domain from St. George's Respiratory Questionnaire (SGRQ-A), the Physical Functioning domain from the SF-36 (SF36-PF), forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and distance walked during a timed walk test (6MWD). Linear regression models were used to examine relationships between UCSD scores and anchors over time.
At baseline, UCSD scores were weakly correlated with percent predicted FVC (−0.21, p=0.005) and percent predicted DLCO (−0.20, p=0.008), moderately correlated with 6MWD (−0.39, p<0.0001) and strongly correlated with SGRQ-A (0.79, p<0.0001) and SF36-PF (−0.72, p<0.0001). Change over time in UCSD scores was associated with change in FVC (estimate=2.54, standard error [SE]=1.23, p=0.04), SGRQ-A (estimate=7.94, SE=1.11, p<0.0001), SF36-PF (estimate=6.00, SE=1.13, p<0.0001), and 6MWD (estimate=4.23, SE=1.18, p=0.0004) but not DLCO (estimate=0.33, SE=1.33, p=0.80).
These results support the validity of the UCSD to assess change in dyspnea over time in patients with IPF.
Limited data are available regarding the role of bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBB) as diagnostic tools in pulmonary Langerhans’ Cell Histiocytosis (LCH) and lymphangioleiomyomatosis (LAM).
The aim of this study was to review our experience regarding the value of these two techniques in the diagnosis of these cystic lung diseases. Records of 452 patients with the presumptive diagnosis of interstitial lung disease were reviewed; 67 had a clinical-radiological diagnosis of either LCH (n=27) or LAM (n= 40). Of 16 patients with LCH who underwent BAL, four specimens (25%) contained cells which had positive immunoreactivity for CD1a. Of three patients with negative BAL fluid who had TBB, only one had a positive tissue diagnosis. Ten LCH patients were diagnosed by surgical lung biopsy of which five had negative BAL fluid. The remaining 12 patients were diagnosed by clinical and radiologic features. Standard examination of BAL fluid was of no diagnostic value in LAM. TBB was performed in seven patients and was diagnostic in six, not resulting in complications. All 13 patients who underwent surgical lung biopsies had a positive histopathologic diagnosis The remaining 21 patients were diagnosed by clinical and radiologic features. We suggest that BAL may assist in the diagnosis of LCH whereas TBB may be useful in the diagnosis of LAM, thus avoiding the need for surgical biopsy.
Interstitial lung diseases; fiberoptic bronchoscopy
We sought to characterize a novel cohort of patients with lung disease, anti-cyclic citrullinated peptide (CCP) antibody positivity, without rheumatoid arthritis (RA) or other connective tissue disease (CTD).
The study sample included 74 subjects with respiratory symptoms, evaluated January 2008–January 2010 and found to have a positive anti-CCP antibody but no evidence for RA or other CTD. Each underwent serologic testing, pulmonary physiology testing, and thoracic high-resolution computed tomography (HRCT) scan as part of routine clinical evaluation.
The majority of subjects were women, and most were former cigarette smokers. Four distinct radiographic phenotypes were identified: isolated airways disease (54%), isolated interstitial lung disease (ILD) (14%), mixed airways disease and ILD (26%), and combined pulmonary fibrosis with emphysema (7%). This cohort had a predominance of airways disease, either in isolation or along with a usual interstitial pneumonia-pattern of ILD. Among subjects with high-titer anti-CCP positivity (n=33), three developed the articular manifestations of RA during a median follow-up of 449 days.
We have described a unique cohort of patients with anti-CCP antibody positivity and lung disease in the absence of existing RA or other CTD. The lung phenotypic characteristics of this cohort resemble those of established RA and a few of these patients have developed articular RA within a short period of follow-up. The implications of a positive anti-CCP antibody among patients with lung disease but not RA are not yet known, but we believe requires further investigation.
Anti-cyclic citrullinated peptide; Rheumatoid arthritis; Interstitial lung disease; Lung diseases
In patients with fibrosing interstitial lung disease (fILD), gastroesophageal reflux (GER) is highly prevalent, perhaps because of the effects of lung fibrosis on altering intrathoracic pressure, diaphragm morphology and lower esophageal sphincter (LES) function. For unclear reasons, obstructive sleep apnea (OSA) is also highly prevalent among patients with fILD. We conducted this study to test our hypothesis that, in patients with fILD, OSA would exacerbate diaphragm/LES dysfunction and increase the propensity for—and severity of—GER.
We identified patients with fILD who underwent screening polysomnogram and pH or pH/impedence probe at our center during the same week. We examined the association between OSA and GER and used logistic regression to determine independent predictors of OSA or GER.
In 54 included subjects, neither OSA (dichotomous) nor apnea hypopnea index (continuous) predicted the presence of GER. Regardless of body position (upright, recumbent), GER was no more frequent or severe among subjects with OSA vs. those without OSA. Subjects with idiopathic pulmonary fibrosis (IPF) had an odds of GER nearly seven-fold greater than subjects with other forms of fILD (odds ratio=6.84, 95% confidence interval 1.36–34.43, p=0.02). For the entire cohort and the subgroup with IPF, there was no correlation between pulmonary physiology and GER.
In fILD, OSA does not appear to promote GER. Research is needed to determine if compensatory mechanisms emanating from the crural diaphragm prevent GER in fILD patients with OSA and to sort out whether GER has a role in the pathogenesis of certain forms of fILD.
Baseline values for daily step counts in US adults with COPD and knowledge of its accurate measurement, natural change over time, and independent relationships with measures of COPD severity are limited.
127 persons with stable COPD wore the StepWatch Activity Monitor (SAM) for 14 days, and 102 of them wore it a median 3.9 months later. SAM counts were compared to manual counts in the clinic. We assessed change over time, the effect of season, and relationships with forced expiratory volume in one second (FEV1) % predicted, 6-minute walk test (6MWT) distance, the modified Medical Research Council (MMRC) dyspnea score, and the St. George’s Respiratory Questionnaire Total Score (SGRQ-TS).
98% of subjects were males, with mean age 71 ± 8 years and FEV1 1.48 ± 0.54 L (52 ± 19 % predicted). All 4 GOLD stages were represented, with the most subjects in GOLD II (44%) and GOLD III (37%). The SAM had > 90% accuracy in 99% of subjects. Average step count was 5,680 steps/day, which decreased with increasing GOLD stage (p=0.0046). Subjects walked 645 fewer steps/day at follow-up, which was partly explained by season of monitoring (p=0.013). In a multivariate model, FEV1 % predicted, 6MWT distance and MMRC score were weakly associated with daily step counts, while SGRQ-TS was not.
These findings will aid the design of future studies using daily step counts in COPD. Accurately measured, daily step counts decline over time partly due to season and capture unique information about COPD status.
Accelerometer; Exercise; Outcomes; Pulmonary Disease
Fibrosis or inflammation of the bronchioles is a well-known manifestation of connective tissue disease (CTD). However, the natural history of CTD-related bronchiolitis is largely unknown.
We analyzed consecutive patients evaluated at National Jewish Health (Denver, CO) from 1998 to 2008 with CTD and surgical lung biopsy-confirmed bronchiolitis. Linear mixed effects models were used to estimate the longitudinal postbronchodilator FEV1 %predicted (%pred) course and differences between subjects with or without constrictive bronchiolitis (CB).
Of 28 subjects with a mean age of 53 ± 9 years, fourteen (50%) had CB. The most common CTD diagnosis was rheumatoid arthritis (n = 14; 50%). There were no significant differences in demographics, smoking status, underlying CTD diagnoses, 6-min walk distance, dyspnea score or drug therapy between subjects with CB and those with cellular bronchiolitis. Three subjects with CB (11%) and four with cellular bronchiolitis (14%) died. Compared with subjects with CB, those with cellular bronchiolitis had higher mean FEV1 %pred at all times. There were no significant differences in FEV1 %pred slope within- or between-groups (CB vs. cellular bronchiolitis) preceding surgical lung biopsy or afterward.
Subjects with CTD-related CB had lower FEV1 %pred values than those with CTD-related cellular bronchiolitis at all time points, but FEV1 %pred remained stable over time in both groups regardless of therapy received.
Pulmonary function testing; Autoimmune disease; Obliterative bronchiolitis
epidemiology; survey; urban health
Idiopathic pulmonary fibrosis (IPF) is a devastating disease that afflicts patients with relentlessly progressive shortness of breath [Joint Statement of the American Thoracic Society and the European Respiratory Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. Am J Respir Crit Care Med 2000;161:646–641]. Despite nearly 30 years of intense investigation, effective therapy for IPF remains elusive; median survival rates have stubbornly remained less than five years from the time of diagnosis [Bjoraker JA, Ryu JH, Edwin MK, Meyers J, Tazelaar H, Schroeder D, et al. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998;157:199–2032, Flaherty KR, Thwaite E, Kazerooni EA, Gross B, Toews GB, Colby TV, et al. Radiological versus histological diagnosis in UIP and NSIP: survival implications. Thorax 2003;58:143–483], and no medical therapy has been proved to be in any way effective for the treatment of this disease. Without medications that help IPF patients live longer, an important question to ask is whether there are interventions that might allow these people to live better—to be more active; to experience less dyspnea, less depression, less anxiety; to possess a greater sense of control over their disease; and to have better quality of life. Pulmonary rehabilitation helps to accomplish many of these goals in patients with chronic obstructive pulmonary disease, and emerging data suggest that it may do the same for patients with IPF.
Pulmonary fibrosis; Pulmonary rehabilitation; Dyspnea
Collection of exhaled breath condensate (EBC) is a non-invasive means of sampling the airway-lining fluid of the lungs. EBC contains numerous measurable mediators, whose analysis could change the management of patients with certain pulmonary diseases.
While initially popularized in investigations involving spontaneously breathing patients, an increasing number of studies have been performed using EBC in association with mechanical ventilation. Collection of EBC in mechanically ventilated patients follows basic principles of condensation, but is influenced by multiple factors. Effective collection requires selection of a collection device, adequate minute ventilation, low cooling temperatures, and sampling times of greater than ten minutes. Condensate can be contaminated by saliva, which needs to be filtered. Dilution of samples occurs secondary to distilled water in vapors and humidification in the ventilator circuit. Dilution factors may need to be employed when investigating non-volatile biomarkers. Storage and analysis should occur promptly at −70° C to −80° C to prevent rapid degradation of samples.
The purpose of this review is to examine and describe methodologies and problems of EBC collection in mechanically ventilated patients. A straightforward and safe framework has been established to investigate disease processes in this population, yet technical aspects of EBC collection still exist that prevent clinical practicality of this technology. These include a lack of standardization of procedure and analysis of biomarkers, and of normal reference ranges for mediators in healthy individuals. Once these procedural aspects have been addressed, EBC could serve as a non-invasive alternative to invasive evaluation of lungs in mechanically ventilated patients.
Exhaled breath condensate; Biomarkers; Inflammation; Mechanical ventilation; Airway-lining fluid
Approximately half the world uses biomass fuel for domestic energy, resulting in widespread exposure to indoor air pollution (IAP) from biomass smoke. IAP has been associated with many respiratory diseases, though it is not clear what relationship exists between biomass use and pulmonary function. Four groups containing 20 households each were selected in Santa Ana, Ecuador based on the relative amount of liquid petroleum gas and biomass fuel that they used for cooking. Pulmonary function tests were conducted on each available member of the households ≥7 years of age. The pulmonary functions of both children (7–15 years) and women (≥16 years) were then compared between cooking fuel categories using multivariate linear regression, controlling for the effects of age, gender, height, and exposure to tobacco smoke. Among the 80 households, 77 children and 91 women performed acceptable and reproducible spirometry. In multivariate analysis, children living in homes that use biomass fuel and children exposed to environmental tobacco smoke had lower forced vital capacity and lower forced expiratory volume in 1 s (P<0:05). However, no significant difference in pulmonary function was observed among women in different cooking categories. Results of this study demonstrate the harmful effects of IAP from biomass smoke on the lung function of children and emphasize the need for public health efforts to decrease exposure to biomass smoke.
Pulmonary function tests; Biomass fuel; Indoor air pollution; Ecuador
In studies of idiopathic pulmonary fibrosis (IPF), whites make up the vast majority of subjects. Whether ethnic/racial differences in idiopathic pulmonary fibrosis occur in the general population is unknown.
To compare the presence of IPF between ethnic/racial groups of U.S. decedents from 1989-2007 by using the National Center for Health Statistics database.
There were 251,058 U.S. decedents with IPF; 87.2% were non-Hispanic whites (White), 5.1% were non-Hispanic African-American (Black), 5.4% were Hispanic, and 2.2% were from other ethnic/racial groups (Other). Whites coded with IPF died older than those in the other groups (77.9 years vs. 72.1 years for Blacks, 75.3 years for Hispanics, and 75.6 years for Others; p<0.0001 for all pairwise comparisons). When controlling for age and for sex, compared with Whites, both Hispanics and Others were more likely to be coded with IPF (OR=1.47, 95% CI 1.44-1.49, p<0.0001 and OR=1.29, 95% CI 1.26-1.36, p<0.0001 respectively), while Blacks were significantly less likely to be coded with IPF (OR=0.48, 95% CI 0.47-0.49, p<0.0001). Among decedents with IPF, Hispanics were more likely, and Blacks were less likely, than Whites to die from IPF (OR=1.24, 95% CI 1.20-1.29, p<0.0001 and OR=0.91, 95% CI 0.87-0.94, p<0.0001).
From 1989-2007, Black decedents were less—and Hispanics were more— likely than Whites to die of/with IPF. Research is needed to determine if genetic differences between ethnic/racial groups explain these findings.
Idiopathic pulmonary fibrosis; mortality; race; epidemiology
Understanding of adolescent-onset asthma remains limited. We sought to characterise this state and identify associated factors within a longitudinal birth cohort study.
The Isle of Wight Whole Population Birth Cohort was recruited in 1989 (N=1456) and characterised at 1, 2, 4, 10 and 18-years. “Adolescent-onset asthma” was defined as asthma at age 18 without prior history of asthma, “persistent-adolescent asthma” as asthma at both 10 and 18 and “never-asthma” as those without asthma at any assessment.
Adolescent-onset asthma accounted for 28.3% of asthma at 18-years and was of similar severity to persistent-adolescent asthma. Adolescent-onset asthmatics showed elevated bronchial hyper-responsiveness (BHR) and atopy at 10 and 18-years. BHR in this group at 10 was intermediate to that of never-asthmatics and persistent-adolescent asthma. By 18 their BHR, bronchodilator reversibility and sputum eosinophilia was greater than never-asthmatics and comparable to persistent-adolescent asthma. At 10, males who later developed adolescent-onset asthma had reduced FEV1 and FEF25–75, while females had normal lung function but then developed impaired FEV1 and FEF25–75 in parallel with adolescent asthma. Factors independently associated with adolescent-onset asthma included atopy at 10 (OR = 2.35; 95% CI = 1.08–5.09), BHR at 10 (3.42; 1.55–7.59), rhinitis at 10 (2.35; 1.11–5.01) and paracetamol use at 18-years (1.10; 1.01–1.19).
Adolescent-onset asthma is associated with significant morbidity. Predisposing factors are atopy, rhinitis and BHR at age 10 while adolescent paracetamol use is also associated with this state. Awareness of potentially modifiable influences may offer avenues for mitigating this disease state.
Adolescence; Asthma; Atopy; Bronchial Hyper-responsiveness; Rhinitis; Paracetamol; Lung Function
Despite efforts to disseminate guidelines for managing chronic obstructive pulmonary disease (COPD), adherence to COPD guidelines remains suboptimal. Barriers to adhering to guidelines remain poorly understood.
Clinicians from two general medicine practices in New York City were surveyed to identify barriers to implementing seven recommendations from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Barriers assessed included unfamiliarity, disagreement, low perceived benefit, low self-efficacy, and time constraints. Exact conditional regression was used to identify barriers independently associated with non-adherence.
The survey was completed by 154 clinicians. Adherence was lowest to referring patients with a forced expiratory volume in one second (FEV1) <80% predicted to pulmonary rehabilitation (5%); using FEV1 to guide management (12%); and ordering pulmonary function tests (PFTs) in smokers (17%). Adherence was intermediate to prescribing inhaled corticosteroids when FEV1 <50% predicted (41%) and long-acting bronchodilators when FEV1 <80% predicted (54%). Adherence was highest for influenza vaccination (90%) and smoking cessation counseling (91%). In unadjusted analyses, low familiarity with the guidelines, low self-efficacy, and time constraints were significantly associated with non-adherence to ≥2 recommendations. In adjusted analyses, low self-efficacy was associated with less adherence to prescribing inhaled corticosteroids (OR: 0.28; 95% CI: 0.10, 0.74) and time constraints were associated with less adherence to ordering PFTs in smokers (OR: 0.31; 95% CI: 0.08, 0.99).
Poor familiarity with recommendations, low self-efficacy, and time constraints are important barriers to adherence to COPD guidelines. This information can be used to develop tailored interventions to improve guideline adherence.
COPD; guidelines; adherence; primary care
Respiratory disorders are more common among farmers than in other populations, despite less atopy and a lower prevalence of smoking; this is likely due to environmental exposure to organic dust and irritants. The current prevalence of respiratory disorders and atopy in Icelandic farmers is unknown, but a significantly greater rate of respiratory symptoms than the general population has been reported in the past. Modern farming practices, which effectively decrease the generation of respirable dust, have been implemented in Iceland in the past decade.
The aim of this study was to estimate the prevalence of respiratory disorders in a nationwide study of Icelandic farmers, and to identify any environmental or occupational associations with these disorders.
We conducted a questionnaire-based study of all Icelandic farmers with an age-matched comparison group randomly selected from the national citizen registry of Iceland. The questionnaire included items regarding respiratory symptoms and working environment.
Out of 2042 farmers invited to participate, 1108 responded (54%), as did 689 of 1500 controls (46%). Farmers were slightly older and more likely to be male (77% vs. 47%). Smoking rates were significantly lower among farmers than among controls. The prevalence of asthma was not significantly different between the two groups, with a lifetime prevalence of 9.4% (n=104) among farmers compared to 10.2% (n=70) among controls. Medication use for asthma did not significantly differ between the farmer (6.5%) and control (4.8%) groups. The prevalence of self-reported, physician-diagnosed chronic bronchitis and emphysema likewise did not significantly differ between the groups, but self-reported “hay fever” was significantly more prevalent among farmers.
Concomitant with changes in farming practices the prevalence of respiratory disorders among Icelandic farmers has decreased. This suggests that modernization of the agricultural environment has a positive effect on workers health.
agriculture; respiratory disorders; farming
In COPD patients, hyperinflation impairs cardiac function. We examined whether lung deflation improves oxygen pulse, a surrogate marker of stroke volume.
In 129 NETT patients with cardiopulmonary exercise testing (CPET) and arterial blood gases (ABG substudy), hyperinflation was assessed with residual volume to total lung capacity ratio (RV/TLC), and cardiac function with oxygen pulse (O2 pulse=VO2/HR) at baseline and 6 months. Medical and surgical patients were divided into “deflators” and “non-deflators” based on change in RV/TLC from baseline (ΔRV/TLC). We defined deflation as the ΔRV/TLC experienced by 75% of surgical patients. We examined changes in O2 pulse at peak and similar (iso-work) exercise. Findings were validated in 718 patients who underwent CPET without ABGs.
In the ABG substudy, surgical and medical deflators improved their RV/TLC and peak O2 pulse (median ΔRV/TLC −18.0% vs. −9.3%, p=0.0003; median ΔO2 pulse 13.6% vs. 1.8%, p=0.12). Surgical deflators also improved iso-work O2 pulse (0.53 mL/beat, p=0.04 at 20 watts). In the validation cohort, surgical deflators experienced a greater improvement in peak O2 pulse than medical deflators (mean 18.9% vs. 1.1%). In surgical deflators improvements in O2 pulse at rest and during unloaded pedaling (0.32 mL/beat, p<0.0001 and 0.47 mL/beat, p<0.0001, respectively) corresponded with significant reductions in HR and improvements in VO2. On multivariate analysis, deflators were 88% more likely than non-deflators to have an improvement in O2 pulse (OR 1.88, 95% CI 1.30–2.72, p=0.0008).
In COPD, decreased hyperinflation through lung volume reduction is associated with improved O2 pulse.
cardiac function; hyperinflation; lung volume reduction surgery; oxygen pulse
Physical activity (PA) has been reported to be reduced in severe chronic obstructive pulmonary disease (COPD). Studies in moderate COPD are currently scarce. The aim of the present study was to investigate physical activity in daily life in patients with COPD (n = 70) and controls (n = 30).
A multi-center controlled study was conducted. PA was assessed using a multisensor armband device (SenseWear, BodyMedia, Pittsburgh, PA) and is reported as the average number of steps per day, and the time spent in mild and moderate physical activity.
Patients suffered from mild (n = 9), moderate (n = 28), severe (n = 23) and very severe (n = 10) COPD. The time spent in activities with mild (80 ± 69 min vs 160 ± 89 min, p < 0.0001) and moderate intensity (24 ± 29 min vs 65 ± 70 min; p < 0.0036) was reduced in patients compared to controls. The number of steps reached 87 ± 34%, 71 ± 32%, 49 ± 34% and 29 ± 20% of control values in GOLD-stages I to IV respectively. The time spent in activities at moderate intensity was 53 ± 47%, 41 ± 45%, 31 ± 47% and 22 ± 34% of the values obtained in controls respectively with increasing GOLD-stage. These differences reached statistical significance as of GOLD stage II (p < 0.05). No differences were observed among centers.
Physical activity is reduced early in the disease progression (as of GOLD-stage II). Reductions in physical activities at moderate intensity seem to precede the reduction in the amount of physical activities at lower intensity.
Physical activity; COPD; Activity monitor; Steps; Energy expenditure
patient recruitment; electronic screening; COPD
The standardized use of a stethoscope for chest auscultation in clinical research is limited by its inherent inter-listener variability. Electronic auscultation and automated classification of recorded lung sounds may help prevent some these shortcomings.
We sought to perform a systematic review and meta-analysis of studies implementing computerized lung sounds analysis (CLSA) to aid in the detection of abnormal lung sounds for specific respiratory disorders.
We searched for articles on CLSA in MEDLINE, EMBASE, Cochrane Library and ISI Web of Knowledge through July 31, 2010. Following qualitative review, we conducted a meta-analysis to estimate the sensitivity and specificity of CLSA for the detection of abnormal lung sounds.
Measurements and Main Results
Of 208 articles identified, we selected eight studies for review. Most studies employed either electret microphones or piezoelectric sensors for auscultation, and Fourier Transform and Neural Network algorithms for analysis and automated classification of lung sounds. Overall sensitivity for the detection of wheezes or crackles using CLSA was 80% (95% CI 72–86%) and specificity was 85% (95% CI 78–91%).
While quality data on CLSA are relatively limited, analysis of existing information suggests that CLSA can provide a relatively high specificity for detecting abnormal lung sounds such as crackles and wheezes. Further research and product development could promote the value of CLSA in research studies or its diagnostic utility in clinical setting.
Pneumonia; Respiratory disorders; Electronic auscultation; Lung sound analysis
Severe hypoxemia is a major complication of chronic obstructive pulmonary disease (COPD). Long term oxygen therapy is beneficial in hypoxemic COPD patients. However, the clinical and radiographic predictors of hypoxemia and the use of oxygen therapy are not well described. This study aimed to find the correlates of resting hypoxemia and the pattern of oxygen use in moderate to severe COPD patients.
Subjects with GOLD stage II or higher COPD from the first 2500 COPDGene subjects were included in this analysis. All subjects were current or ex-smokers between ages 45 and 80. Severe resting hypoxemia was defined as room air oxygen saturation (SpO2) ≤ 88%. Use of supplemental oxygen therapy was determined by questionnaire.
Eighty-two of 1060 COPD subjects (7.7%) had severe resting hypoxemia. Twenty-one of the 82 (25.6%) were not using continuous supplemental oxygen. Female sex, higher BMI, lower FEV1, and enrollment in Denver were independent risk factors for hypoxemia; emphysema severity on quantitative chest CT scan did not predict hypoxemia. 132 of 971(13.6%) subjects without severe resting hypoxemia were using continuous supplemental oxygen. In non-hypoxemic oxygen users, Denver recruitment, higher BMI, lower FEV1, and more severe dyspnea were associated with the use of continuous oxygen.
A large number of COPD patients without severe hypoxemia were using supplemental oxygen therapy and the pattern of oxygen use was affected by factors other than resting SpO2 and emphysema severity. Longitudinal data will be required to reveal the effects of oxygen therapy in this subgroup.
Hypoxemia; long-term oxygen therapy; COPD; emphysema
Previously, we reported that prenatal exposures to polycyclic aromatic hydrocarbons (PAH) and postnatal environmental tobacco smoke (ETS) in combination were associated with respiratory symptoms at ages 1 and 2 years. Here, we hypothesized that children exposed to both prenatal PAH and ETS may be at greater risk of asthma and seroatopy at ages 5 to 6 years, after controlling for current pollution exposure.
Prenatal PAH exposure was measured by personal air monitoring over 48 hrs. ETS exposure, respiratory symptoms and asthma at ages 5–6 years were assessed through questionnaire. Immunoglobulin (Ig) E was measured by Immunocap.
A significant interaction between prenatal PAH and prenatal (but not postnatal) ETS exposure on asthma (p<0.05), but not IgE, was detected. Among children exposed to prenatal ETS, a positive nonsignificant association was found between prenatal PAH exposure and asthma (OR 1.96, 95% CI [0.95–4.05]). Among children without exposure to prenatal ETS, a negative nonsignificant association was found between prenatal PAH exposure and asthma (OR 0.65, 95% CI [0.41–1.01]). Prenatal PAH exposure was not associated with asthma or IgE at age 5 to 6 years.
Combined prenatal exposure to PAH and ETS appears to be associated with asthma but not seroatopy at age 5–6. Exposure to PAH alone does not appear associated with either asthma or seroatopy at age 5 to 6 years. Discerning the differential effects between ETS exposed and ETS nonexposed children requires further study.
To investigate incidence, risk factors and impact of falls on health related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD).
Observational cohort study
Patients completed these questionnaires at baseline and at 6-months: Medical Outcomes Study Short Form 36 (SF-36), Chronic Respiratory Questionnaire (CRQ), Activities Balance Confidence (ABC) Scale and a form to record demographic data, medications, co-morbidities, oxygen use, acute exacerbations, fall history and assistive device use. Physical activity was measured with the Physical Activity Scale for the Elderly (PASE) only at baseline. Fall incidence was monitored through monthly fall diaries. Patients were categorized as non-fallers (0 falls) or fallers (≥1 falls).
Data from 101 patients with a forced expiratory volume in one second of 46.4±21.6% predicted were analyzed. Thirty-two patients (31.7%) reported at least one fall during the 6-months. Fall incidence rate was 0.1 (95% CI:0.06 to 0.14) falls per person-month. Fallers tended to be older (p=0.04), female (p=0.04) and oxygen dependent (p=0.02), have a history of previous falls (p<0.001), more co-morbidities (p=0.007) and take more medications (p=0.001). Previous falls (OR=7.36; 95% CI:2.39 to 22.69) and diagnosis of coronary heart disease (OR=7.07; 95% CI:2.14 to 23.36) were the most important predictors of falls. The Dyspnea Domain of the CRQ declined significantly more (p=0.02) in the fallers group at 6-months.
Patients with COPD have a high susceptibility to falls, which is associated with a worsening of dyspnea perception as related to HRQoL. Fall prevention programs in COPD are recommended.
PMID: 20869227 CAMSID: cams2186
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality caused by cigarette smoking and other environmental exposures. While variation in exposures may affect COPD morbidity and mortality, little is known about geographic variation, a surrogate of exposures. The objective of this manuscript is to explore the geographic variation in COPD hospitalization rates among the Texas population in 2006.
The study population consisted of all Texas residents with COPD hospitalizations in the 2006 Texas Health Care Information Council (THCIC) data. County population estimates stratified by race, age, gender were linked to THCIC data to calculate county level COPD hospitalization rates per 100,000 admissions. The data were merged with Urban Influence Codes by county, and metropolitan status was determined by United States Department of Agriculture (USDA) criteria. Variation in COPD hospitalization rates were analyzed using Poisson Regression.
Overall, non-Hispanic (NH) Whites had the highest rate of hospitalization, followed by NH Blacks (rate ratio=0.42) and Hispanics (RR=0.17), the 65+ age category had the highest rates of hospitalization. In the metropolitan counties COPD hospitalization rates are lower than non metropolitan counties, however in metropolitan counties the rates of hospitalization are significantly higher (p<0.0001) in females compared to males. The rates were significantly higher in males in public health regions 10 and 11, which are predominantly non-metropolitan counties.
In Texas there is substantial geographic variation in hospitalization rates associated with gender and race/ethnicity. Other factors that may contribute to the variation and require further investigation include differences in smoking and exposure to other environmental risk factors, access to primary care, medical practice patterns, and coding practices.
In asthma, cysteinyl leukotrienes (CysLTs) play varying roles in the bronchomotor response to multiple provocative stimuli. The contribution of CysLTs on the airway's response to hypertonic saline (HS) inhalation in asthma is unknown. Whether polymorphisms in the leukotriene biosynthetic pathway affect the contribution of CysLTs to this response is also unknown.
In a prospective, randomized, double blind, placebo-controlled cross-over study, mild and moderate asymptomatic asthmatics underwent inhaled 3% HS challenge by doubling the duration of nebulization (0.5, 1, 2, 4, and 8 min) two hours after one dose of montelukast (a CysLT receptor 1 [CysLTR1] antagonist) or placebo, and after three week courses. We examined the effect of the leukotriene C4 synthase (LTC4S) polymorphism (A-444C) on the efficacy of montelukast against HS inhalation in an exploratory manner.
In 37 subjects, two hours after administration of montelukast, the mean provocative dose of HS required to cause a 20% drop in FEV1 (HS-PD20) increased by 59% (9.17 after placebo vs. 14.55 ml after montelukast, p = 0.0154). Three weeks of cysLTR1 antagonism increased the HS-PD20 by 84% (10.97 vs. 20.21 ml, p = 0.0002). Three weeks of CysLTR1 antagonism appeared to produce greater effects on blocking bronchial hyper responsiveness (two hour vs. three week HS-PD20 values 14.55 vs. 20.21 ml respectively, p = 0.0898). We did not observe an effect of the LTC4S polymorphism on the response to CysLTR1 antagonism in this cohort.
A significant proportion of HS-induced bronchoconstriction is mediated by release of leukotrienes as evidenced by substantial acute inhibition with a CysLTR1 antagonist. There was a trend toward greater inhibition of bronchial responsiveness with three weeks of therapy as opposed to acute CysLTR1 antagonism.
Asthma; Leukotriene-C4 synthase; Montelukast; Polymorphism, Single Nucleotide; Saline Solution, Hypertonic
Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible chronic airflow obstruction and by an accelerated decline in lung function. Elevated circulating levels of C-reactive protein (CRP) and interleukin-6 (IL-6), both markers of systemic inflammation, have been found in COPD. Their possible associations with chronic airflow obstruction have mostly been evaluated in highly selected patient samples. Our objective was to evaluate the association between postbronchodilator lung function CRP and IL-6 in a randomly selected sample of the Icelandic population, 40 years and older, while adjusting for gender, age, smoking, and body weight.
Serum CRP and IL-6 values were measured among participants in the Burden of Obstructive Lung Disease (BOLD) study.
Of the 938 subjects invited a total of 403 men and 355 women participated (response rate 81%) in the study. Their mean age (±SD) was 57.7 (±12.7) years. Both CRP and IL-6 were independently related to lower FEV1 and FVC values. Individuals in the highest quartiles of CRP and IL-6 had a 7.5% and 3.9%, respectively, lower FEV1% than predicted after adjustment for smoking, age, and body weight. High CRP levels were more strongly related to lower FEV1 levels in men (−11.4%) than in women ( −0.4%).
In a random population-based sample both CRP and IL-6 were significantly related to lower spirometric values. The association with CRP was stronger in men than in women. This finding underscores the possible importance of systemic inflammation in irreversible airflow limitation.
Airflow obstruction; Systemic inflammation; Cytokines; C-reactive protein; IL-6
Chronic obstructive pulmonary disease (COPD) is a respiratory disease that results in airflow limitation and respiratory distress. The effects of COPD, however, are not exclusively limited to respiratory function and people with COPD face many non-respiratory manifestations that affect both function and mobility. Deficits in function and mobility have been associated with an increased risk for falling in older adults. The purpose of this study was to provide a theoretical framework to identify risks factors for falls in people with COPD. We have analyzed the literature to identify possible relationships between pathophysiological changes observed in COPD and common risk factors for falls. Well-established fall risk factors in people with COPD include lower limb muscle weakness and impaired activities of daily living. Other intrinsic risk factors such as gait and balance deficits, nutritional depletion, malnutrition, depression, cognitive impairments and medications are possible risk factors that need to be confirmed with more studies. There is no evidence that visual deficits are common in COPD. The role that precipitating factors such as syncope and postural hypotension may have on fall risk is unclear. Exacerbations and dyspnea do not have a precipitating effect on fall risk but they contribute to the progressive physical deterioration that may theoretically increase the risk for falls. While these results suggest that people with COPD might have an increased susceptibility to fall compared to their healthy peers, further research is needed to determine the prevalence of falls and specific risk factors for falls in people living with COPD.
PMID: 19419852 CAMSID: cams2185