BACKGROUND

Anion gap metabolic acidosis is typically encountered in the emergency department (ED) setting as the result of shock, other endogenous metabolic derangements, or from exogenous toxicants. The differential diagnosis for toxicant-related acidosis (exemplified by common mnemonics) emphasizes acute overdose.

CASE REPORT

The case we present manifested an anion gap (AG) metabolic acidosis due to a chronic intoxication: acetaminophen (APAP) overuse over a period of weeks. Lactic acidemia did not account for the AG. In this case, chronic APAP overuse, combined with decreased caloric intake and weight loss, was associated with excess 5-oxoproline (pyroglutamic acid), an organic acid accounting for the AG metabolic acidosis. Overproduction of 5-oxoproline is attributed to depleted glutathione stores, leading to perturbation in the γ-glutamyl cycle. The patient was treated with supportive care and with N-acetylcysteine (NAC). By repleting glutathione, NAC may facilitate the resolution of excess 5-oxoproline.

CONCLUSIONS

The ED differential diagnosis of AG metabolic acidosis in chronic APAP overuse, especially with concomitant nutritional compromise, should include 5-oxoprolinemia.

BACKGROUND

Information is scant assessing outcomes in lung transplantation (LT) in advanced occupational lung diseases (OLD).

AIMS

To analyse survival after LT for OLD.

METHODS

Using data from the US Organ Procurement and Transplantation Network Registry (OPTN-R), we identified subjects aged ≥ 18 years transplanted for OLD from 2005 to 2010. OPTN-R selected referents of corresponding age, sex and body mass index (BMI) who underwent LT for other diagnoses were also identified. Post-LT survival time was estimated with Cox proportional hazard models. Baseline age, BMI, forced expiratory volume in 1 s, creatinine, lung allocation score, donor age, donor lung ischaemic time and transplant type (single versus bilateral) were included as covariates. Time-dependent covariates were used to model differences in relative risk over time.

RESULTS

Thirty-seven males underwent LT for silicosis (n = 19) or other OLD (n = 18) during the analytic period (0.5% of all LTs). For non-silicotic OLD, 6-month and 1- and 3-year survival estimates were 66, 55 and 55%, compared with the silicotic group (86, 86 and 76%) and referent group (89, 84 and 67%). During the first year post-transplant, those with OLD (silicosis and others combined) manifested an overall 2-fold increased mortality risk [hazard ratio (HR) 2.3, 95% CI 1.3-4.4; P < 0.05] compared to referents. In stratified analysis, this increased risk of death was restricted to those with non-silicotic OLD (HR 3.1, 95% CI 1.5-6.6; P < 0.01). Poorer survival was limited to the first year post-LT.

CONCLUSIONS

Subjects undergoing LT for OLD other than silicosis may be at increased risk of death in the first year post-transplantation.

INTRODUCTION

The clinical scenario of a new or worsening pleural effusion following the initiation of antituberculous therapy has been classically referred to as a 'paradoxical' pleural response, presumably explained by an immunological rebound phenomenon. Emerging evidence suggests that there also may be a role for a lupus-related reaction in the pathophysiology of this disorder.

CASE PRESENTATION

An 84-year-old Asian man treated with isoniazid, along with rifampin, pyrazinamide and ethambutol for suspected extrapulmonary tuberculosis, presented with a recurrent pleural effusion, his third episode since the initiation of this therapy. The first effusion occurred one month after the start of treatment, without any prior evidence of pulmonary tuberculosis involvement. Follow-up testing, including thoracoscopic pleural biopsies, never confirmed tuberculosis infection. Further evaluation yielded serological evidence suggesting drug-induced lupus. No effusions recurred following the discontinuation of isoniazid, although other antituberculosis medications were continued.

CONCLUSION

The immunological rebound construct is inconsistent with the evolution of this case, which indicates rather that drug-induced lupus may explain at least some cases of new pleural effusions following the initiation of isoniazid.

OBJECTIVE

To investigate the cross-sectional association between COPD severity and disturbed sleep and the longitudinal association between disturbed sleep and poor health outcomes.

METHODS

Ninety eight adults with spirometrically-confirmed COPD were recruited through population-based, random-digit telephone dialing. Sleep disturbance was evaluated using a 4-item scale assessing insomnia symptoms as: difficulty falling asleep, nocturnal awakening, morning tiredness, and sleep duration adequacy. COPD severity was quantified by: FEV(1) and COPD Severity Score, which incorporates COPD symptoms, requirement for COPD medications and oxygen, and hospital-based utilization. Subjects were assessed one year after baseline to determine longitudinal COPD exacerbations and emergency utilization and were followed for a median 2.4 years to assess all-cause mortality.

RESULTS

Sleep disturbance was cross-sectionally associated with cough, dyspnea, and COPD Severity Score, but not FEV(1). In multivariable logistic regression, controlling for sociodemographics and body-mass index, sleep disturbance longitudinally predicted both incident COPD exacerbations (OR=4.7; p=0.018) and respiratory-related emergency utilization (OR=11.5; p=0.004). In Cox proportional hazards analysis, controlling for the same covariates, sleep disturbance predicted poorer survival (HR=5.0; p=0.013). For all outcomes, these relationships persisted after also controlling for baseline FEV(1) and COPD Severity Score.

CONCLUSIONS

Disturbed sleep is cross-sectionally associated with worse COPD and is longitudinally predictive of COPD exacerbations, emergency health care utilization, and mortality.

BACKGROUND

Obesity contributes to respiratory symptoms and exercise limitation, but the relationships between obesity, airflow obstruction (AO), respiratory symptoms and functional limitation are complex.

AIMS

To determine the relationship of obesity with airflow obstruction (AO) and respiratory symptoms in adults without a previous diagnosis of chronic obstructive pulmonary disease (COPD).

METHODS

We analysed data for potential referents recruited to be healthy controls for an ongoing study of COPD. The potential referents had no prior diagnosis of COPD or healthcare utilisation attributed to COPD in the 12 months prior to recruitment. Subjects completed a structured interview and a clinical assessment including body mass index, spirometry, six-minute walk test (SMWT), and the Short Performance Physical Battery (SPPB). Multiple regression analyses were used to test the associations of obesity (body mass index >30 kg/m2) and smoking with AO (forced expiratory volume in 1s/forced vital capacity ratio <0.7). We also tested the association of obesity with respiratory symptoms and impaired functional capacity (SPPB, SMWT), adjusting for AO.

RESULTS

Of 371 subjects (aged 40-65 years), 69 (19%) had AO. In multivariate analysis, smoking was positively associated with AO (per 10 pack-years, OR 1.24; 95% CI 1.04 to 1.49) while obesity was negatively associated with AO (OR 0.54; 95% CI 0.30 to 0.98). Obesity was associated with increased odds of reporting dyspnoea on exertion (OR 3.6; 95% CI 2.0 to 6.4), productive cough (OR 2.5; 95% CI 1.1 to 6.0), and with decrements in SMWT distance (67 ± 9 m; 95% CI 50 to 84 m) and SPPB score (OR 1.9; 95% CI 1.1 to 3.5). None of these outcomes was associated with AO.

CONCLUSIONS

Although AO and obesity are both common among adults without an established COPD diagnosis, obesity (but not AO) is linked to a higher risk of reporting dyspnoea on exertion, productive cough, and poorer functional capacity.

BACKGROUND

Although chronic obstructive pulmonary disease (COPD) is a major cause of disability worldwide, its determinants remain poorly defined.

OBJECTIVE

We hypothesized that both pulmonary and extra-pulmonary factors would predict prospective disablement across a hierarchy of activities in persons with COPD.

METHODS

Six hundred and nine participants were studied at baseline (T0) and 2.5 years later (T1). The Valued Life Activities (VLA) scale quantified disability (10-point scale: 0 = no difficulty and 10 = unable to perform), defining disability as any activity newly rated 'unable to perform' at T1. Predictors included pulmonary (lung function, 6-minute walk distance and COPD severity score) and extra-pulmonary (quadriceps strength and lower extremity function) factors. Prospective disability risk was tested by separate logistic regression models for each predictor (baseline value and its change, T0-T1; odds ratios were scaled at 1 standard deviation per factor. Incident disability across a hierarchy of obligatory, committed and discretionary VLA subscales was compared.

RESULTS

Subjects manifested a 40% or greater increased odds of developing disability for each predictor (baseline and change over time). Disability in discretionary activities developed at a rate 2.2-times higher than observed in committed activities, which was in turn 2.5-times higher than the rate observed in obligatory activities (p < 0.05 for each level).

CONCLUSIONS

Disability is common in COPD. Both pulmonary and extra-pulmonary factors are important in predicting its development.

OBJECTIVE

To assess the contribution of workplace exposures to chronic obstructive pulmonary disease (COPD) risk in a community with a heavy burden of past industrial employment.

METHODS

A random population sample of Sheffield, U.K. residents aged over 55 years (n=4000), enriched with a hospital-based supplemental sample (n=209), was approached for study. A comprehensive self-completed questionnaire elicited physician-made diagnoses, current symptoms, and past workplace exposures. The latter were defined in three ways: self-reported exposure to vapours, gases, dusts and fumes (VGDF); response to a specific exposure checklist; and through a job exposure matrix (JEM) assigning exposure risk likelihood based on job history independent of respondent-reported exposure. A subset of the study group underwent lung function testing. Population attributable risk fractions (PAR%), adjusted for age, sex and smoking, were calculated for association between workplace exposure and COPD.

RESULTS

2001 (50%) questionnaires were returned from the general population sample and 60 (29%) by the hospital supplement. Among 1754 with complete occupational data, any past occupational exposure to VGDF carried an adjusted excess risk for report of a physician's diagnosis of COPD, emphysema, or chronic bronchitis (ORs 3.9; 95% CI 2.7 to 5.8), with a corresponding PAR% value of 58.7% (95% CI 45.6% to 68.7%). The PAR% estimate based on JEM exposure was 31%. From within the subgroup of 571 that underwent lung function testing, VGDF exposure was associated with a PAR% of 20.0% (95% CI -7.2 to 40.3%) for Global initiative for chronic obstructive lung disease (GOLD) 1 (or greater) level of COPD.

CONCLUSION

This heavy industrial community-based population study has confirmed significant associations between reported COPD and both generic VGDF and JEM-defined exposures. This study supports the predominantly international evidence-based notion that workplace conditions are important when considering the current and future respiratory health of the workforce.

BACKGROUND

Silicosis is a progressive, fibrotic, occupational lung disease resulting from inhalation of respirable crystalline silica. This disease is preventable through appropriate workplace practices. We systematically assessed an outbreak of silicosis among patients referred to our center for lung transplant.

METHODS

This retrospective cohort analysis included all patients with a diagnosis of silicosis who were referred for evaluation to the National Lung Transplantation Program in Israel from January 1997 through December 2010. We also compared the incidence of lung transplantation (LTX) due to silicosis in Israel with that of the International Society for Heart and Lung Transplantation (ISHLT) registry.

RESULTS

During the 14-year study period, 25 patients with silicosis were referred for evaluation, including 10 patients who went on to undergo LTX. All patients were exposed by dry cutting a relatively new, artificial, decorative stone product with high crystalline silica content used primarily for kitchen countertops and bathroom fixtures. The patients had moderate-to-severe restrictive lung disease. Two patients developed progressive massive fibrosis; none manifested acute silicosis (silicoproteinosis). Three patients died during follow-up, without LTX. Based on the ISHLT registry incidence, 0.68 silicosis cases would have been expected instead of the 10 observed (incidence ratio, 14.6; 95% CI, 7.02-26.8).

CONCLUSIONS

This silicosis outbreak is important because of the worldwide use of this and similar high-silica-content, artificial stone products. Further cases are likely to occur unless effective preventive measures are undertaken and existing safety practices are enforced.

BACKGROUND

Limited health literacy is associated with poor outcomes in many chronic diseases, but little is known about health literacy in chronic obstructive pulmonary disease (COPD).

OBJECTIVE

To examine the associations between health literacy and both outcomes and health status in COPD. PARTICIPANTS, DESIGN AND MAIN MEASURES: Structured interviews were administered to 277 subjects with self-report of physician-diagnosed COPD, recruited through US random-digit telephone dialing. Health literacy was measured with a validated three-item battery. Multivariable linear regression, controlling for sociodemographics including income and education, determined the cross-sectional associations between health literacy and COPD-related health status: COPD Severity Score, COPD Helplessness Index, and Airways Questionnaire-20R [measuring respiratory-specific health-related quality of life (HRQoL)]. Multivariable logistic regression estimated associations between health literacy and COPD-related hospitalizations and emergency department (ED) visits.

KEY RESULTS

Taking socioeconomic status into account, poorer health literacy (lowest tertile compared to highest tertile) was associated with: worse COPD severity (+2.3 points; 95 % CI 0.3-4.4); greater COPD helplessness (+3.7 points; 95 % CI 1.6-5.8); and worse respiratory-specific HRQoL (+3.5 points; 95 % CI 1.8-4.9). Poorer health literacy, also controlling for the same covariates, was associated with higher likelihood of COPD-related hospitalizations (OR = 6.6; 95 % CI 1.3-33) and COPD-related ED visits (OR = 4.7; 95 % CI 1.5-15). Analyses for trend across health literacy tertiles were statistically significant (p < 0.05) for all above outcomes.

CONCLUSIONS

Independent of socioeconomic status, poor health literacy is associated with greater COPD severity, greater COPD helplessness, worse respiratory-specific HRQoL, and higher odds of COPD-related emergency health-care utilization. These results underscore that COPD patients with poor health literacy may be at particular risk for poor health-related outcomes.