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.

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.

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.

Factors affecting outcomes of individualised treatment for drug resistant tuberculosis in an endemic region.

BACKGROUND: Individualised treatment regimens for drug resistant tuberculosis have improved outcomes. This retrospective observational study examined potential factors that affect individualised treatment in an endemic region, and highlighted predictors of a successful outcome. METHODS: We examined records of proven MDR, pre-XDR and XDR TB patients diagnosed and started on treatment between 2010 and 2014, and collected the following data for each patient: age, gender, comorbidities, past history of TB, diagnosis, site of disease, drug susceptibility testing (DST) results, treatment, adverse reactions to anti-tubercular drugs, treatment changes and outcomes, which were recorded as positive, negative or neutral. Tests of association were carried out between factors and outcomes, following which multiple logistic regression analysis was done to determine the predictors of a positive outcome such as patient cured after completion of treatment at 18 months or longer. RESULTS: Fifty-nine patients completed treatment at our centre. The median age was 26 years (range 8-65 years). There were 31 (52.5%) female patients. Forty-four (74.6%) were successfully treated over a median treatment period of 23 months (range 18-30 months). Successful outcomes were associated with age less than 45 years (P=0.01, OR=6.67, 95% CI=1.73-23.47), resistance to fewer than five drugs (P=0.001, OR=9.51, 95% CI=2.50-38.18) and susceptibility to Group 4 drugs (P=0.04, OR=4.71, 95% CI=1.03-16.83). CONCLUSIONS: Age and drug susceptibility were important predictors of treatment outcome.

Combined pirfenidone, azithromycin and prednisolone in post-H1N1 ARDS pulmonary fibrosis.

There are no specific data on the management of pulmonary fibrosis post-H1N1 ARDS. We present the cases of three patients who responded positively to treatment with pirfenidone, azithromycin and prednisolone. Three males, aged 40, 45 and 59 years, had H1N1 ARDS requiring mechanical ventilation for two weeks or longer. After weaning off ventilation, they had persistent symptoms and hypoxemia at rest despite receiving prednisolone and home oxygen for at least three weeks following discharge. Computed tomography (CT) of the chest showed fibrosis and traction bronchiectasis. At presentation, they could not perform spirometry. Investigations ruled out infection. Pirfenidone (600 mg daily escalated to maximum tolerable dose of 2.4 gm daily) and azithromycin (500 mg thrice weekly) were added off-label to prednisolone. In one patient pirfenidone was discontinued after three months due to an adverse reaction and azithromycin was continued for nine months. At one year follow-up, all patients had symptomatic improvement, better effort tolerance, regression of opacities and no progression of fibrosis on CT, and improvement in spirometry and six minute walk tests. Pirfenidone and azithromycin added to prednisolone may have led to clinical and radiological improvement. The current experience suggests that this treatment approach to pulmonary fibrosis post-H1N1 ARDS be studied further. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 85-90).

Inconsistency in the reporting of antitubercular drug susceptibility tests in an endemic region.

BACKGROUND: Individualized treatment for multidrug-resistant tuberculosis (MDR TB) is associated with improved outcomes. Therapy needs to be tailored to drug susceptibility testing (DST) results. We present our observations on the inconsistency in DST reporting in an endemic region with a high prevalence of MDR TB. METHODS: We retrospectively analyzed 118 DST reports from 10 different laboratories. OBSERVATIONS: Of 118 patients, only 79 (67%) had DST reports with results to all first-line drugs, a fluoroquinolone (excluding ciprofloxacin), all aminoglycosides, and a polypeptide. Twenty-one (18%) isolates did not have DST reports for all first-line drugs; 4 (3%) did not have DST reports for any second-line drugs; 9 (8%) did not have DST reports for a fluoroquinolone; and 31 (26%) did not have DST reports for all second-line aminoglycosides and polypeptide. CONCLUSION: Inconsistencies were observed in several of the 118 DST reports. A case is made for sensitization toward standardization and completeness in TB DST reporting in India.

Bronchoscopic and surgical management of rare endobronchial tumors.

Pure endobronchial neoplasms are a rare entity, and they may present with diverse pathological findings. Malignant diseases are more common than benign ones, and they mostly originate from the surface epithelium. Endobronchial tumors usually present with symptoms such as cough, hemoptysis, recurrent pneumonia, wheezing, and chest pain. Flexible bronchoscopy is necessary for diagnosis and evaluation of these endobronchial tumors. Advance bronchoscopy or definitive surgery is the modality of treatment for these tumors based on the presentation. We present a case series of patients suffering from different rare endobronchial tumors and their management along with the review of literature.

Diagnostic value of core biopsy histology and cytology sampling of mediastinal lymph nodes using 21-gauge EBUS-TBNA needle.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the initial modality of choice in sampling mediastinal lymphadenopathy. It is possible to obtain both cytological and histological samples using both 21-gauge and 22-gauge EBUS-TBNA needles. The current study was undertaken to compare the diagnostic yield of cytology and histology samples obtained by the same EBUS-TBNA 21-gauge needle. PATIENTS AND METHODS: One hundred sixty-six consecutive patients who underwent EBUS-TBNA with a 21-gauge EBUS-TBNA needle over a period of 3 years were included in this retrospective analysis. The diagnostic yields of EBUS-TBNA histology (EBUS-TBNA-H) and EBUS-TBNA cytology (EBUS-TBNA-C) specimens were compared using the McNemar test. RESULTS: The overall sensitivity and specificity of EBUS-TBNA were 89% and 100%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of EBUS-TBNA were 100% and 53%, respectively. The overall sensitivity and specificity of EBUS-TBNA-H were 85% and 100%, respectively. The PPV and NPV of EBUS-TBNA-H were 100% and 43%, respectively. The overall sensitivity and specificity of EBUS-TBNA-C were 65% and 100%, respectively. The PPV and NPV of EBUS-TBNA-C were 100% and 14%, respectively. The diagnostic yield of EBUS-TBNA-H over EBUS-TBNA-C was statistically significant (P < 0.0001). CONCLUSION: EBUS-TBNA-H with 21-gauge needle significantly improves the diagnostic yield of EBUS-TBNA. EBUS-TBNA-H improves the NPV of EBUS-TBNA. The combination of EBUS-TBNA-H and EBUS-TBNA-C improves the overall diagnostic yield of EBUS-TBNA.