Long-Term Exposure to House Dust Mite Leads to the Suppression of Allergic Airway Disease Despite Persistent Lung Inflammation.

BACKGROUND: Allergic asthma is a major cause of worldwide morbidity and results from inadequate immune regulation in response to innocuous, environmental antigens. The need exists to understand the mechanisms that promote nonreactivity to human-relevant allergens such as house dust mite (HDM) in order to develop curative therapies for asthma. The aim of our study was to compare the effects of short-, intermediate- and long-term HDM administration in a murine asthma model and determine the ability of long-term HDM exposure to suppress allergic inflammation. METHODS: C57BL/6 mice were intranasally instilled with HDM for short-term (2 weeks), intermediate-term (5 weeks) and long-term (11 weeks) periods to induce allergic airway disease (AAD). The severity of AAD was compared across all stages of the model via both immunological and pulmonary parameters. RESULTS: Short- and intermediate-term HDM exposure stimulated the development of AAD that included eosinophilia in the bronchoalveolar lavage fluid (BALF), pronounced airway hyperreactivity (AHR) and evidence of lung inflammation. Long-term HDM exposure promoted the suppression of AAD, with a loss of BALF eosinophilia and AHR despite persistent mononuclear inflammation in the lungs. Suppression of AAD with long-term HDM exposure was associated with an increase in both Foxp3+ regulatory T cells and IL-10-positive alveolar macrophages at the site of inflammation. CONCLUSIONS: This model recapitulates the key features of human asthma and may facilitate investigation into the mechanisms that promote immunological tolerance against clinically relevant aeroallergens.

Biopsy proven interstitial nephritis following treatment with vancomycin: a case report.

Acute interstitial nephritis is rarely reported with vancomycin. Literature searches revealed six biopsy-proven cases of vancomycin-induced interstitial nephritis. We report a case of a 51-year-old male who was treated with vancomycin and gentamicin for primary osteomyelitis with methicillin resistant Staphyloccocus aureus bacteremia. He developed rash and acute kidney injury after vancomycin therapy. Renal function continued to decline despite discontinuation of vancomycin and prednisone was initiated. Rapid improvement of kidney function was noted and the patient was discharged with an improved creatinine. There was a failure of compliance with steroid therapy, and a second episode of acute kidney injury developed. Creatinine again improved after restarting steroids. Physicians should consider interstitial nephritis when patients are on vancomycin even when they have been on the medication for weeks. Although there have been no controlled clinical trials on the efficacy of steroids in acute interstitial nephritis, it should still be considered if improvement is not evident after drug withdrawal.

A longitudinal study evaluating the effect of exacerbations on physical activity in patients with chronic obstructive pulmonary disease.

BACKGROUND: Physical inactivity is common in stable chronic obstructive pulmonary disease (COPD) and independently predicts poor outcomes. Longitudinal assessments of physical activity in outpatients with COPD, covering periods of stability and exacerbations, have not been evaluated previously. METHODS: Patients with clinically stable COPD and a history of two or more clinical exacerbations in the preceding 12 months were recruited. Physical activity was measured using a triaxial accelerometer worn continuously on the nondominant wrist. Mean minutes per day of higher level physical activity was the primary outcome variable. Symptom-defined exacerbations were assessed using the 14-item Exacerbations of Chronic Pulmonary Disease Tool (EXACT) daily dairy. Clinically reported exacerbations were also captured. Minutes per day of higher level physical activity during exacerbation and nonexacerbation days were compared, using a mixed model analysis. MEASUREMENTS AND MAIN RESULTS: Seventeen patients were monitored for 135 ± 18 days. Nine were male with a mean age of 63 ± 12 years and mean FEV1 of 52 ± 20%. Fifteen patients had 27 symptom (EXACT)-defined exacerbations, including 9 that were also clinically reported. Patients spent fewer minutes per day at a higher level physical activity level during exacerbation days than nonexacerbation days: 131 ± 14 versus 157 ± 14 minutes (P < 0.0001). The greatest reduction in physical activity was during the first week of the exacerbation; activity remained low for approximately 2 weeks after exacerbation resolution. CONCLUSIONS: Physical activity decreased significantly during exacerbations. Reduction in activity occurs early during an exacerbation and persists for about 2 weeks after symptomatic recovery.

Physiologic responses during the six minute walk test in obese and non-obese COPD patients.

Although obesity is a common co-morbid condition in COPD, relatively little is known how it may affect functional exercise capacity. Accordingly, we compared physiologic responses during a 6 min walk test in 10 obese and 10 non-obese COPD patients matched by gender, age, and spirometric severity category. Patients first exercised on a treadmill to determine maximal exercise responses, then following a rest period they completed a 6 min walk test. Breath by-breath analyses of expired air via a facemask was obtained using a portable, battery operated device. Oxygen consumption (VO(2)), carbon dioxide production (VCO(2)), tidal volume (VT), respiratory rate (RR), minute ventilation (VE), and inspiratory capacity (IC) were compared. The mean FEV1 in the obese and non-obese groups was 52 ± 13 and 58 ± 18 percent of predicted, respectively, and the BMI of the obese patients was 37 ± 02 kg/m(2). Obese patients had shorter 6 min walk distances than non-obese patients (247 ± 73 vs 348 ± 51 m, respectively, p = 0.003), but walk-work, defined as 6 min walk distance × weight (in kg), was not different. There were no significant between-group differences in any exercise variable measured during the 6 min walk test. In both groups, VO(2) and VE increased linearly over the first 2-3 min, then plateaued at approximately 80% of maximum. Although 6 min walk distance is shorter in obese COPD patients, their physiologic responses are similar to those of non-obese patients.