Occupational asthma and work-exacerbated asthma: factors associated with time to diagnostic steps

BACKGROUND: Little is known regarding the factors associated with the times for patients' first physician visit, the first physician suspicion of work-related asthma (WRA), and final diagnosis after the onset of WRA symptoms. This study examined individual and work-related factors that are associated with longer times to these diagnostic milestones among groups with occupational asthma (OA) and work-exacerbated asthma (WEA). METHOD: Suspected WRA cases were identified from an occupational lung disease clinic and claimants to the Ontario Workplace Safety and Insurance Board (100 patients each). Questionnaire administration and chart review were undertaken. RESULTS: Eighty participants were classified as having sensitizer-induced OA and 87 as having WEA. For the OA group, the risk factors for delay included male sex, being unmarried, low education, and lack of awareness of association of symptoms with work. Other factors included older age, being the sole income earner, and lack of knowledge of the Workplace Hazardous Materials Information System program. For WEA, lower household income, lower education, absence of a health-and-safety program at work, absence of a union, and lack of awareness of OA and of agents at work that could affect asthma significantly increased the time to diagnostic milestones. CONCLUSIONS: Different factors affect the diagnostic milestones for OA and WEA. Findings suggest a need for educational programs for workers who are at risk of OA and WEA and a need for further primary care physician education on WRA.     

Biological lung volume reduction: a new bronchoscopic therapy for advanced emphysema

BACKGROUND: Biological lung volume reduction (BLVR) using biological reagents to remodel and shrink damaged regions of lung has previously been accomplished in sheep with experimental pulmonary emphysema. This report summarizes the initial clinical experience including a 3-month follow-up using this technique in humans. METHODS: An open-label phase 1 trial designed to evaluate the safety of BLVR in patients with advanced heterogeneous emphysema enrolled six patients. Of these, three patients received unilateral treatment at two pulmonary subsegments (group 1) and three patients received unilateral treatment at four pulmonary subsegments (group 2). The incidence of adverse events and changes in pulmonary function test results, symptoms, and exercise capacity were evaluated. RESULTS: The mean (+/- SD) age of the six men enrolled in the study was 66 +/- 5.7 years (age range, 57 to 73 years). BLVR was well tolerated in both treatment groups and was not associated with any serious complications. All patients were discharged from the hospital on posttreatment day 1. Although the primary purpose of the study was to examine safety, improvements were observed in mean vital capacity (+7.2 +/- 9.5%; range, -2% to + 19%), mean residual volume (RV) [-7.8 +/- 8.5%; range, + 1% to -22%], mean RV/total lung capacity ratio (-6.6 +/- 4.7%; range, -1% to -15%), mean 6-min walk distance (+14.5 +/- 18.5%; range, 0 to + 51%), and in mean dyspnea score. On average, group 2 patients experienced greater benefit from BLVR than group 1 patients, suggesting a dose-response pattern. CONCLUSIONS: Preliminary results indicate that BLVR can be safe and may produce benefits in appropriately selected patients with advanced heterogeneous emphysema.     

Sleep and well-being of ICU housestaff

BACKGROUND: Our understanding of the effect of the Accreditation Council for Graduate Medical Education (ACGME)-mandated work-hour limitation on physicians' quality of life, sleepiness, and sleep-work habits is evolving. In this study, we sought to determine the effect of work-hour reduction on quality of life in residents and fellows (ICU housestaff) when subject to the ACGME-compliant schedule of one institution. To determine the effect of work-hour reduction on subjective and objective measures of sleepiness in ICU housestaff at a center. METHODS: A single-center study of 34 residents and 10 fellows who were studied before and after the ACGME-mandated work-hour limitation went into effect in July 2003. RESULTS: In a single center, after the work-hour reduction, residents reported statistically significant but minor improvements in sleep time, subjective sleepiness, and some aspects of quality of life (p < 0.05). Both before and after work-hour limitations, subjective sleepiness and quality-of-life indexes deteriorated during the course of the ICU rotation. Following work-hour reductions, subjective sleepiness improved (p < 0.05), but objective sleepiness was unchanged (p = 0.6). Moreover, after the implementation of work-hour reductions, 59%, 43%, and 25% of the ICU team had mean sleep latency < 10, 7, and 5 min, respectively, with 14% of the team manifesting sleep-onset rapid eye movement periods (signifying severe sleepiness) before beginning their extended work-hour period. CONCLUSIONS: In ICU housestaff, at a single center, small benefits to quality of life and subjective sleepiness were realized by an ACGME-compliant work-hour schedule. Significant levels of objective sleepiness, however, remained. Further measures may need to be undertaken to address the persistence of sleepiness in ICU housestaff. These findings may not be generalized outside of the scheduling system studied.     

A pooled analysis of FEV1 decline in COPD patients randomized to inhaled corticosteroids or placebo

BACKGROUND: There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV(1). METHODS: The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven long-term randomized controlled trials of ICS vs placebo lasting >/= 12 months in patients with moderate-to-severe COPD. We have previously reported a survival benefit for ICS therapy in COPD patients using ISEEC data. We aimed to determine whether the regular use of ICSs vs placebo improves FEV(1) decline in COPD patients, and whether this relationship is modified by gender and smoking. RESULTS: There were 3,911 randomized participants (29.2% female) in this analysis. In the first 6 months after randomization, ICS use was associated with a significant mean (+/- SE) relative increase in FEV(1) of 2.42 +/- 0.19% compared with placebo (p < 0.01), which is quantifiable in absolute terms as 42 mL in men and 29 mL in women over 6 months. From 6 to 36 months, there was no significant difference between placebo and ICS therapy in terms of FEV(1) decline (-0.01 +/- 0.09%; p = 0.86). The initial treatment effect was dependent on smoking status and gender. Smokers who continued to smoke had a smaller increase in FEV(1) during the first 6 months than did ex-smokers. Female ex-smokers had a larger increase in FEV(1) with ICS therapy than did male ex-smokers. CONCLUSIONS: We conclude that in COPD in the first 6 months of treatment, ICS therapy is more effective in ex-smokers than in current smokers with COPD in improving lung function, and women may have a bigger response to ICSs than men. However, it seems that after 6 months, ICS therapy does not modify the decline in FEV(1) among those who completed these randomized clinical trials.     

Early changes of cardiac structure and function in COPD patients with mild hypoxemia

BACKGROUND: COPD is often associated with changes of the structure and the function of the heart. Although functional abnormalities of the right ventricle (RV) have been well described in COPD patients with severe hypoxemia, little is known about these changes in patients with normoxia and mild hypoxemia. STUDY OBJECTIVES: To assess the structural and functional cardiac changes in COPD patients with normal Pa(O2) and without signs of RV failure. METHODS: In 25 clinically stable COPD patients (FEV1, 1.23 +/- 0.51 L/s; Pa(O2), 82 +/- 10 mm Hg [mean +/- SD]) and 26 age-matched control subjects, the RV and left ventricular (LV) structure and function were measured by MRI. Pulmonary artery pressure (PAP) was estimated from right pulmonary artery distensibility. RESULTS: RV mass divided by RV end-diastolic volume as a measure of RV adaptation was 0.72 +/- 0.18 g/mL in the COPD group and 0.41 +/- 0.09 g/mL in the control group (p < 0.01). LV and RV ejection fractions were 62 +/- 14% and 53 +/- 12% in the COPD patients, and 68 +/- 11% and 53 +/- 7% in the control subjects, respectively. PAP estimated from right pulmonary artery distensibility was not elevated in the COPD group. CONCLUSION: From these results, we conclude that concentric RV hypertrophy is the earliest sign of RV pressure overload in patients with COPD. This structural adaptation of the heart does not alter RV and LV systolic function.     

Endobronchial ultrasound

During flexible fiberoptic bronchoscopy (FB), a solitary pulmonary nodule (SPN) is sampled by means of transbronchial needle aspiration (TBNA), brush, or transbronchial lung biopsy under fluoroscopy; and mediastinal lymph nodes are sampled using "blind" TBNA. Endobronchial ultrasound (EBUS) was developed to help visualize the lesion at the time of biopsy in order to improve the diagnostic yield. METHODS: There are two types of EBUS techniques: using a radial probe (RP) with a rotating transducer at the distal tip, which produces a 360 degrees image to the long axis of the bronchoscope; and using an EBUS bronchoscope with a linear transducer at its distal tip, producing a 50 degrees image parallel to its long axis. RESULTS: In biopsies of SPNs < 2 cm using an RP, EBUS demonstrates a higher diagnostic yield than conventional FB techniques. With mediastinal and hilar nodal stations, except for the subcarina, EBUS shows a higher yield over blind TBNA. The current procedural terminology code for EBUS is 31620, a "ZZZ" code submitted in addition to other performed procedures (31622-31638). In 2007, an estimate of physician Medicare reimbursement for EBUS is $70.49. Reimbursement is locality dependent and based on economic-exchange conversion factors. Incorporating an ultrasound image into the report substantiates the use of this technique. Limitations: The physician must learn ultrasound image interpretation and the EBUS technique, and be skilled in TBNA. Maintaining competency requires frequent performance of EBUS. CONCLUSION: EBUS-directed biopsy improves the yield over conventional FB for SPNs < 2 cm and for most mediastinal or hilar nodal stations. This reduces the need to conduct additional diagnostic procedures.     

An evaluation of a titration strategy for prescription of oral appliances for obstructive sleep apnea

BACKGROUND: Oral appliances (OAs) are first-line therapy for mild-to-moderate obstructive sleep apnea (OSA) and are being used with increasing frequency. Additionally, best practice of OA titration is unknown. We describe the experience of patients treated with an OA, identify factors that predict treatment success with an OA, and offer a protocol for OA titration. METHODS: We retrospectively studied patients seen in a dental sleep clinic between 2002 and 2006. Patients selected for OA treatment underwent baseline polysomnography, were individually fit with an OA, and were instructed to titrate it at home until symptom resolution or discomfort. During follow-up polysomnography, additional titration was performed as needed. Primary outcome was successful treatment, defined as apnea-hypopnea index (AHI) <10 events per hour and AHI decrease at least 50% from baseline. Logistic regression models were created to identify associations between patient characteristics and successful treatment. Overall differences in AHI at baseline, after home titration, and after final titration were compared using Kruskal-Wallis test, and post hoc comparisons were performed with sign tests, with Bonferroni corrections. RESULTS: Of 57 subjects treated with an OA, 37 subjects (64.9%) were successfully treated with OA therapy. Of the 49 subjects for whom data were available for AHI after home titration, 27 subjects (55%) achieved successful treatment of OSA by self-titration, without need for further titration during follow-up polysomnography. CONCLUSIONS: A majority of subjects, regardless of OSA severity, are successfully treated with an OA. Men and younger patients were found to be the best responders. The titration protocol for an OA offers a beneficial initial step in the treatment of OSA.     

Effect of a gonadotrophin-releasing hormone analogue on lung function in lymphangioleiomyomatosis

BACKGROUND: Lymphangioleiomyomatosis (LAM), a multisystem disease occurring primarily in women, is characterized by cystic lung destruction, and kidney and lymphatic tumors, caused by the proliferation of abnormal-appearing cells (ie, LAM cells) with a smooth muscle cell phenotype that express melanoma antigens and are capable of metastasizing. Estrogen receptors are present in LAM cells, and this finding, along with reports of disease progression during pregnancy or following exogenous estrogen administration, suggest the involvement of estrogens in the pathogenesis of LAM. Consequently, antiestrogen therapies have been employed in treatment. The goal of this prospective study was to evaluate the efficacy of triptorelin, a gonadotrophin-releasing hormone analogue, in 11 premenopausal women with LAM. METHODS: Patients were evaluated at baseline and every 3 to 6 months thereafter, for a total of 36 months. Hormonal assays, pulmonary function tests, 6-min walk tests, high-resolution CT scans of the chest, and bone mineral density studies were performed. RESULTS: Gonadal suppression was achieved in all patients. Overall, a significant decline in lung function was observed; two patients underwent lung transplantation 1 year after study enrollment, and another patient was lost to follow-up. Treatment with triptorelin was associated with a decline in bone mineral density. CONCLUSIONS: Triptorelin appears not to prevent a decline in lung function in patients with LAM. Its use, however, may be associated with the loss of bone mineral density.     

Differences in airway cytokine profile in severe asthma compared to moderate asthma

BACKGROUND: Some studies of severe asthma suggest that persistence or alteration in the pattern of inflammation may be associated with the severity of the disease. Whether there are differences in the expression of the principal cytokines and chemokines relevant to eosinophilic and neutrophilic inflammation in the airway tissues of severe compared to moderate asthmatics has not been determined. The aim of this study was to compare the patterns of expression of representative T-helper (Th) type 1 (interferon [IFN]-gamma) and Th-2 cytokines (interleukin [IL]-4, IL-5) and the neutrophil- and eosinophil-associated chemokines (IL-8 and eotaxin) in the airway tissues of patients with severe and moderate asthma. METHODS: Subjects with severe asthma (n = 24) and a comparison moderate asthma group (n = 26) were assessed using spirometry, induced sputum, exhaled nitric oxide, and bronchial biopsy. The expression of proteins of interest in the epithelium and subepithelium of the airway wall was examined by immunocytochemistry. RESULTS: Subjects with severe asthma were more symptomatic, had a lower FEV(1), and had more sputum neutrophilia (p = 0.007) and eosinophilia (p = 0.001). Exhaled nitric oxide was similar between groups. IL-8 and IFN-gamma expression were increased and IL-4 expression was decreased in severe asthma compared to moderate disease (p < 0.001 for each comparison). Eotaxin and IL-5 expression did not differ between the groups. CONCLUSION: Patients with severe asthma have increases in neutrophils and eosinophils in the sputum, and differ in airway cytokine/chemokine expression from moderate asthmatics. Excess neutrophilia may be explained by increased expression of IL-8, but differences in eosinophilia do not appear to be associated with IL-5 and eotaxin expression.     

Timeliness of care in veterans with non-small cell lung cancer

BACKGROUND: Timeliness is an important dimension of quality of care for patients with lung cancer. METHODS: We reviewed the records of consecutive patients in whom non-small cell lung cancer (NSCLC) had been diagnosed between January 1, 2002, and December 31, 2003, at the Veterans Affairs Palo Alto Health Care System. We used multivariable statistical methods to identify independent predictors of timely care and examined the effect of timeliness on survival. RESULTS: We identified 129 veterans with NSCLC (mean age, 67 years; 98% men; 83% white), most of whom had adenocarcinoma (51%) or squamous cell carcinoma (30%). A minority of patients (18%) presented with a solitary pulmonary nodule (SPN). The median time from the initial suspicion of cancer to treatment was 84 days (interquartile range, 38 to 153 days). Independent predictors of treatment within 84 days included hospitalization within 7 days (odds ratio [OR], 8.2; 95% confidence interval [CI], 2.9 to 23), tumor size of > 3.0 cm (OR, 4.8; 95% CI, 1.8 to 12.4), the presence of additional chest radiographic abnormalities (OR, 3.0; 95% CI, 1.1 to 8.5), and the presence of one or more symptoms suggesting metastasis (OR, 2.6; 95% CI, 1.1 to 6.2). More timely care was not associated with better survival time (adjusted hazard ratio, 1.6; 95% CI, 1.3 to 1.9). However, in patients with SPNs, there was a trend toward better survival time when the time to treatment was < 84 days. CONCLUSIONS: The time to treatment for patients with NSCLC was often longer than recommended. Patients with larger tumors, symptoms, and other chest radiographic abnormalities receive more timely care. In patients with malignant SPNs, survival may be better when treatment is initiated promptly.