High Incidence of New-Onset Joint Pain in Patients on Fluoroquinolones as Antituberculous Treatment.

BACKGROUND: Joint pain is frequently observed in patients on antituberculous treatment, and pyrazinamide is known to be associated with joint pain in patients receiving antituberculous treatment. Fluoroquinolone-associated joint pain and tendon injury have been reported in long-term corticosteroid and transplant recipients, but data are lacking in patients with tuberculosis. OBJECTIVES: The objective of this study was to examine the incidence of joint pain manifested during administration of antituberculous therapy and their association with fluoroquinolones. METHODS: Patients diagnosed with tuberculosis attending the outpatient clinic over a period of 1 year were reviewed and divided into 3 groups: group A receiving pyrazinamide, group B receiving a fluoroquinolone, and group C receiving both pyrazinamide and a fluoroquinolone. Latency to onset of joint pain was noted in all 3 groups. Joint pain was initially managed with analgesics, and associated hyperuricemia was treated with allopurinol/febuxostat. Causative drugs were stopped in case of intolerable joint pain. RESULTS: 260 patients (47% females, aged 38 ± 18 years; mean ± SD) were included [group A (n = 140), group B (n = 81), and group C (n = 39)]. Overall, 76/260 (29%) patients developed joint pain: group A - 24/140 patients (17%), group B - 32/81 patients (40%), and group C - 20/39 patients (51%). The median latency to the onset of joint pain was 83 days (interquartile range, IQR 40-167): 55 days (IQR 32-66) in group A, 138 days (IQR 74-278) in group B, and 88 days (IQR 34-183) in group C. Hyperuricemia was present in 12/24 (50%) patients in group A and 11/20 (55%) patients in group C. Pyrazinamide was stopped in 7/140 (5%) patients in group A, fluoroquinolones in 6/81 (7%) patients in group B, and both pyrazinamide and fluoroquinolones were stopped in 5/39 (13%) patients in group C because of intolerable joint pain. Major joints affected were knees and ankles. CONCLUSION: There is a high incidence of joint pain in patients receiving antituberculous treatment, which is higher when fluoroquinolones or the pyrazinamide-fluoroquinolone combination are administered as compared to pyrazinamide alone.

[Interventionen beim Asthma COPD]. / Interventions In Asthma and COPD.

Advanced emphysema and asthma constitute major health burden worldwide and are associated with significant morbidity and mortality. Pharmacological options are limited. Researches are being carried out aiming to modify the natural course of both the diseases. Lung volume reduction surgeries are performed in advanced emphysema but are associated with significant morbidity and prolonged hospital stay. Various minimally invasive bronchoscopic methods have been developed with the goal of achieving clinical benefits of volume reduction surgery but lower complications. Bronchial thermoplasty is a bronchoscopic method of delivering controlled heat in the airways to reduce airway smooth muscle mass, thereby reducing bronchoconstriction in patients with severe asthma who remain uncontrolled despite optimal medical therapy. Various randomised controlled trials have been performed to evaluate the safety and efficacy of various endoscopic treatments like valves, coils, use of sclerosants and targeted lung denervation for severe emphysema and bronchial thermoplasty in severe asthma. The current review summaries the clinical trial evidence available for lung volume reduction in emphysema and thermoplasty in asthma and provide guidance for optimal patient selection for various therapies available.

Factors Affecting Best-Tolerated Dose of Pirfenidone in Patients with Fibrosing Interstitial Lung Disease.

The aim of the study was to examine the best-tolerated dose of pirfenidone, the adverse effects profile, and potential factors other than drug dose influencing the tolerability of pirfenidone in patients with fibrosing interstitial lung diseases (ILDs). We performed an observational retrospective study of 113 patients with IPF and other fibrosing ILDs treated with pirfenidone. Baseline liver function tests (LFTs) and dose escalation of pirfenidone were recorded for all patients. The best-tolerated dose was continued if the patient did not tolerate full dose (2400 mg) despite repeated dose escalation attempts. Potential risk factors such as age, height, weight, body mass index (BMI), body surface area (BSA), gender, smoking, and presence of comorbidities were analyzed between 3 groups of best-tolerated pirfenidone doses: 2400 mg/day vs. <2400 mg/day, 2400 mg/day vs. 1800 mg/day, and 2400 mg/day vs. 1200 mg/day. A total of 24 patients tolerated 2400 mg/day, and 89 patients tolerated <2400 mg/day (43 tolerated 1800 mg/day, 45 tolerated 1200 mg/day and 1 tolerated 600 mg/day). Patients who tolerated 2400 mg/day were taller and had a larger BSA as compared to those tolerating <2400 mg/day. Overall, males tolerated the drug better. Presence of comorbidities or smoking did not affect the tolerance of pirfenidone, except for the presence of cerebrovascular diseases. Various adverse effects did not have any significantly different frequencies between the compared groups. Moreover, 71.7% of patients experienced at least one side effect. 1200 mg/day was the best-tolerated dose in the majority of the patients. Male patients with a larger BSA and greater height showed better tolerability of pirfenidone overall.

EBUS-TBNA in the rapid microbiological diagnosis of drug-resistant mediastinal tuberculous lymphadenopathy.

This study aimed to examine the use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the rapid diagnosis of mediastinal tuberculous lymphadenitis and drug-resistant mediastinal tuberculous lymphadenitis. A diagnosis of TB was confirmed by a positive Xpert MTB/RIF test or Mycobacterium tuberculosis culture. Rifampicin-resistant TB (RR-TB) or multidrug-resistant TB (MDR-TB) was diagnosed upon the detection of rifampicin resistance by Xpert MTB/RIF or resistance to rifampicin and isoniazid by phenotypic drug susceptibility testing (DST). Xpert MTB/RIF was positive in 43 of 56 patients (77%) and TB culture was positive in 31 of 56 patients (55%). Of these 56 patients, 25 (45%) were Xpert MTB/RIF positive and TB culture negative, 13 (23%) were Xpert MTB/RIF negative and TB culture positive, and 18 (32%) were Xpert MTB/RIF positive and TB culture positive. 11 patients (20%) had drug-resistant TB: seven with RR/MDR-TB, one with pre-extensively drug-resistant (XDR) TB, two with XDR-TB and one with isoniazid mono-resistance. An Xpert MTB/RIF assay carried out on EBUS-TBNA specimens provides rapid diagnosis of TB. Xpert MTB/RIF testing appears to have additional and more rapid sensitivity compared with culture alone. Culture-based DST provides an additional exclusive yield and the full resistance profile in addition to or instead of rifampicin resistance.