BACKGROUND

Separate health-related quality of life (HRQL) instruments exist for asthma and rhinitis. The Rhinasthma questionnaire, originally developed in Italian, is a unique measure designed for use where both conditions coexist.

OBJECTIVE

We sought to assess the performance and validity of a new adaptation of the Rhinasthma questionnaire for use in English-speaking populations.

METHODS

We analyzed cross-sectional data from an ongoing study of adults with asthma and rhinitis (n = 450), asthma alone (n = 75), or rhinitis alone (n = 20). Subjects were administered an English translation of the original 30-item Rhinasthma questionnaire. Health status measures simultaneously assessed include the Short Form (SF)-12, EuroQol (EQ)-5D, and Marks Asthma Quality-of-Life.

RESULTS

Variable cluster analysis of the original 30-item instrument identified 5 discrete item clusters corresponding to the following domains: nasal (5 items), eye (4 items), respiratory (5 items), activity restriction (9 items), and treatment burden (5 items). Two other items were removed because of poor item-cluster correlations. Subjects with concomitant asthma and rhinitis had greater HRQL impairment, as measured by the Rhinasthma, than subjects with either asthma or rhinitis alone. The Rhinasthma correlated significantly (P < .05) with the SF-12, EQ-5D, and Marks Asthma Quality-of-Life in the anticipated direction consistent with the underlying constructs. In multiple logistic regression, poorer Rhinasthma HRQL was associated with significantly (P < .05) increased odds of both asthma- and rhinitis-related disability even after taking into account physical health status as measured by the SF-12.

CONCLUSION

The 28-item English adaptation of Rhinasthma performs well in assessing HRQL in patients with asthma, rhinitis, or both conditions combined.

Studies systematically comparing the performance of health-related quality-of-life (HRQoL) instruments in pulmonary arterial hypertension (PAH) are lacking. We sought to address this by comparing cardiac and respiratory-specific measures of HRQoL in PAH. We prospectively assessed HRQoL in 128 patients with catheterisation-confirmed PAH at baseline and at 6, 12 and post-24 month follow-up visits. Cardiac-specific HRQoL was assessed using the Minnesota Living with Heart Failure Questionnaire (LHFQ); respiratory-specific HRQoL was assessed using the Airways Questionnaire 20 (AQ20); and general health status was assessed using the 36-item Short Form physical component summary (SF-36 PCS). The LHFQ and AQ20 were highly intercorrelated. Both demonstrated strong internal consistency and converged with the SF-36 PCS. Both discriminated patients based on World Health Organization (WHO) functional class, 6-min walking distance (6MWD) and Borg dyspnoea index (BDI), with the exception of a potential floor effect associated with low 6MWD. The LHFQ was more responsive than the AQ20 to changes over time in WHO functional class, 6MWD and BDI. In multivariate analyses, the LHFQ and AQ20 were each longitudinal predictors of general health status, independent of functional class, 6MWD and BDI. In conclusion, both cardiac-specific and respiratory-specific measures appropriately assess HRQoL in most patients with PAH. Overall, the LHFQ demonstrates stronger performance characteristics than the AQ20.

A recurrent clinical dilemma in the management of patients with painful metastatic lesions is achieving a balance between effective analgesic therapies versus intolerable side effects, in particular altered mental status. We present the case of an immunosuppressed patient post-lung transplant who was suffering from intractable pain caused by widely metastatic squamous cell carcinoma. The patient's progressive, excruciating neuropathic pain was localized to the area of the left wrist and forearm. Additionally, the patient complained of moderate pain at sites of tumor involvement on her right arm and scalp. Attempts to adequately manage her left upper extremity pain included a combination of pharmacologic treatments intended to treat neuropathic pain (gabapentin, SNRI, ketamine, opioids) and focused regional analgesia (infraclavicular infusion of local anesthetic). However, the patient developed intolerable side effects including altered mental status and delirium associated with the systemic agents and suboptimal control with the infraclavicular infusion. Given that the most severe pain was well localized, we undertook a diagnostic block of the cutaneous nerves of the left forearm. As this intervention significantly reduced her pain, we subsequently performed neurectomies to the left superficial radial nerve, lateral cutaneous nerve of the forearm and the posterior cutaneous nerve of the forearm. This resulted in immediate and continued relief of her left upper extremity pain without an altered mental status. Residual focal pain from lesions over her right arm and scalp was successfully managed with daily topical applications of lidocaine and capsaicin cream. Successful pain control continued until the patient's death five months later.

PURPOSE

We sought to quantify the impact of respiratory muscle and lower extremity strength on exercise capacity and lower extremity function (LEF) in patients with chronic obstructive pulmonary disease (COPD).

METHODS

In 828 persons with COPD, we assessed the impact of reduced respiratory (maximum inspiratory pressure, MIP) and lower extremity muscle strength (quadriceps strength, QS) on exercise capacity (6-minute walk test, 6MWT), and LEF (short physical performance battery). Multiple regression analyses taking into account key covariates, including lung function and smoking, tested the associations between muscle strength and exercise and functional capacity.

RESULTS

For each 0.5 SD decrement in QS, men walked 18.3 m less during 6MWT (95% confidence interval [CI], -24.1 to -12.4); women 25.1 m less (95% CI, -31.1 to -12.4). For each 0.5 SD decrement in MIP, men walked 9.4 m less during 6MWT (95% CI, -15.2 to -3.6); women 8.7 m less (95% CI, -14.1 to -3.4). For each 0.5 SD decrease in QS, men had a 1.32 higher odds (95% CI, 1.11-1.15) of poor LEF; women had a 1.87 higher odds (95% CI, 1.54-2.27). Lower MIP (per 0.5 SD) was associated with increased odds of poor LEF in women (odds ratio = 1.18; 95% CI, 1.00-1.39), but not in men (odds ratio = 1.10; 95% CI, 0.93-1.31).

CONCLUSIONS

In COPD, reduced respiratory and lower extremity muscle strength are associated with decreased exercise and functional capacity. Muscle weakness is likely an important component of impairment and disability in patients with COPD.

BACKGROUND

Matrix metalloproteinase-9 (MMP-9) may be important in the progression of emphysema, but there have been few longitudinal clinical studies of MMP-9 including pulmonary status and COPD exacerbation outcomes.

METHODS

We utilized data from the placebo arm (n=126) of a clinical trial of patients with alpha1-antitrypsin deficiency (AATD) and emphysema to examine the links between plasma MMP-9 levels, pulmonary status, and COPD exacerbations over a one year observation period. Pulmonary function, computed tomography lung density, incremental shuttle walk test (ISWT), and COPD exacerbations were assessed at regular intervals over 12 months. Prospective analyses used generalized estimating equations to incorporate repeated longitudinal measurements of MMP-9 and all endpoints, controlling for age, gender, race-ethnicity, leukocyte count, and tobacco history. A secondary analysis also incorporated highly-sensitive C-reactive protein levels in predictive models.

RESULTS

At baseline, higher plasma MMP-9 levels were cross-sectionally associated with lower FEV1 (p=0.03), FVC (p<0.001), carbon monoxide transfer factor (p=0.03), resting oxygen saturation (p=0.02), and ISWT distance walked (p=0.02) but were not associated with radiographic lung density or total lung capacity (TLC). In longitudinal analyses, MMP-9 predicted a further decline in transfer factor (p=0.04) and oxygen saturation (p<0.001). MMP-9 also predicted worsening lung density (p=0.003), increasing TLC (p=0.02), and more frequent COPD exacerbations over follow-up (p=0.003). Controlling additionally for hs-CRP levels did not substantively change the longitudinal associations between MMP-9 and these outcomes.

CONCLUSIONS

Increased plasma MMP-9 levels generally predicted pulmonary status declines, including worsening transfer factor and lung density as well as greater COPD exacerbations in AATD-associated emphysema.

INTRODUCTION

People with α1-antitrypsin deficiency are at increased risk for the development of chronic obstructive pulmonary disease. Previous retrospective epidemiologic studies have found that exposure to occupational dust among those with α1-antitrypsin deficiency is a risk factor at the group level for poorer lung function, but on an individual clinical basis, a causal attribution can be difficult to establish.

CASE PRESENTATION

We describe the case of a 68-year-old Caucasian man with a 25 pack-year smoking history who presented with new-onset dyspnea on exertion in the setting of workplace dust exposure. During his evaluation, he was found to have α1-antitrypsin deficiency with evidence of development of pulmonary emphysema. Workplace spirometric monitoring over 10 years of surveillance for an on-the-job respirator fit program demonstrated a sharp downward slope in forced expiratory volume in one second, or FEV1, during his periods of most significant dust exposure, which was attenuated after discontinuation of his workplace exposure.

CONCLUSION

Patients with α1-antitrypsin disease should be assessed for occupational exposures and closely monitored for work-accelerated progression of lung function decline. More generally, this case report supports the biological plausibility of occupationally associated chronic obstructive pulmonary disease, underscoring that work-associated pulmonary disease can be multi-factorial.

PURPOSE

: The independent contribution of physical inactivity to disability in obstructive lung disease (OLD) is difficult to study, partly because inactivity may reflect disease severity. We examined the relationship of physical inactivity to disability progression over a 1-year period among a group of older adults with OLD.

METHODS

: A population-based cohort with self-reported physician-diagnosed emphysema, chronic obstructive pulmonary disease, or chronic bronchitis (n = 206) completed baseline interviews and in-person spirometry, with 1-year followup interviews. The Community Health Activities Model Program for Seniors physical activity questionnaire provided estimates of energy expenditure; we defined inactivity as no expenditure in moderate- or vigorous-intensity activities. Disability was measured with the Valued Life Activity (VLA) disability scale; increased disability was defined as a 10% or greater increase in VLA disability score over 1-year followup. Logistic regression tested the relationship between baseline inactivity and disability increase, controlling for age, sex, baseline VLA disability, comorbidities, smoking, and pulmonary function (forced expiratory volume in 1 second, % predicted).

RESULTS

: Of 206 subjects, 48 (27%) were physically inactive at baseline; 42.9% of individuals whose disability increased were inactive at baseline compared with 23.4% of those who did not experience a disability increase. With adjustment for covariates, increased disability after 1 year was significantly (P = .04) more likely among individuals who were inactive at baseline (Odds Ratio =2.4; 95% confidence interval, 1.02-5.9).

CONCLUSIONS

: Physically inactive individuals with OLD had more than double the odds of an increase in disability, even after controlling for baseline disability, lung function, and other covariates. These results provide strong support for the importance of maintaining physical activity among individuals with OLD.

Development of asthma and allergic inflammation involves innate immunity, but the environmental contributions remain incompletely defined. Analysis of dust collected from the homes of asthmatic individuals revealed that the polysaccharide chitin is environmentally widespread and associated with β-glucans, possibly from ubiquitous fungi. Cell wall preparations of Aspergillus isolated from house dust induced robust recruitment of eosinophils into mouse lung, an effect that was attenuated by enzymatic degradation of cell wall chitin and β-glucans. Mice expressing constitutively active acidic mammalian chitinase in the lungs demonstrated a significant reduction in eosinophil infiltration after fungal challenge. Conversely, chitinase inhibition prolonged the duration of tissue eosinophilia. Thus, fungal chitin derived from home environments associated with asthma induces eosinophilic allergic inflammation in the lung, and mammalian chitinases, including acidic mammalian chitinase, limit this process.

Lung transplantation in mechanically ventilated (MV) patients has been associated with decreased posttransplant survival. Under the Lung Allocation Score (LAS) system, patients at greatest risk of death on the waiting list, particularly those requiring MV, are prioritized for lung allocation. We evaluated whether pretransplant MV is associated with poorer posttransplant survival in the LAS era. Using a national registry, we analyzed all adults undergoing lung transplantation in the United States from 2005 to 2010. Propensity scoring identified nonventilated matched referents for 419 subjects requiring MV at the time of transplantation. Survival was evaluated using Kaplan-Meier methods. Risk of death was estimated by hazard ratios employing time-dependent covariates. We found that pretransplant MV was associated with decreased overall survival after lung transplantation. In the first 6 months posttransplant, ventilated subjects had a twofold higher risk of death compared to nonventilated subjects. However, after 6 months posttransplant, survival did not differ by MV status. We also found that pretransplant MV was not associated with decreased survival in noncystic fibrosis obstructive lung diseases. These results suggest that under the LAS, pretransplant MV is associated with poorer short-term survival posttransplant. Notably, the increased risk of death appears to be strongest the early posttransplant period and limited to certain pretransplant diagnoses.

BACKGROUND AND AIMS

This review summarizes the scientific literature relevant to occupational risk factors for chronic obstructive pulmonary disease (COPD).

MATERIAL AND METHODS

This review emphasizes recent work in the field, while placing this in the context of two previous systematic reviews of the subject.

RESULTS

Both the earlier summaries of the literature estimated that the population attributable risk percent (PAR%) of COPD linked to occupational exposures is approximately 15%. More recent studies also strongly support the association between workplace exposures and COPD. Among never smokers, the PAR% for work-related factors may approach 40%. Emerging data also indicate that occupational exposures, at a minimum, are additive to smoking-associated risk of COPD.

CONCLUSIONS

The PAR% for work-related COPD is at least 15%. Scientific significance. The consistency, strength, and plausibility of these data support a causal relationship between occupational exposures and COPD.