HIV and COPD: a conspiracy of risk factors.

Chronic obstructive pulmonary disease (COPD) is an under recognized complication of HIV infection. It is estimated that up to 25% of HIV infected people may have COPD. HIV is associated with COPD as a result of a complex interplay of multiple factors such as pulmonary inflammation, recurrent pulmonary infections especially tuberculosis (TB), increased cigarette smoking, socio-economic status, childhood respiratory illnesses and industrial and environmental exposures; each of which are risk factors for COPD in their own right. COPD presents at an earlier age in people with HIV infection. There are over 35 million people living with HIV, and most people infected with HIV live in developing regions of the world where they are faced with multiple risk factors for COPD and suboptimal access to health care. TB is the commonest infectious complication of HIV, and HIV infected persons often experience multiple episodes of TB. Cigarette smoking is increasing in developing countries where the greatest burden of TB and HIV is experienced. Cigarette smoking is associated with increased risk of TB and may be associated with acquisition of HIV infection and progression. It is not clear whether non-infectious pulmonary inflammation persists in the lung when immune reconstitution occurs. Prevention and control of HIV infection must be part of the multiple interventions to reduce the global burden of COPD. A multidisciplinary approach, including behavioural science is required to address this challenge. It presents research opportunities that should be driven by the pulmonology community.

Over-prescription of short-acting ß2-agonists is associated with poor asthma outcomes: results from the African cohort of the SABINA III study.

BACKGROUND: The extent of short-acting ß2-agonist (SABA) overuse in Africa remains poorly documented. As part of the SABA use IN Asthma (SABINA) III study, we assessed SABA prescriptions/clinical outcomes in 3 African countries. METHODS: Data on disease characteristics/asthma treatments were collected from patients (≥12 years) using electronic case report forms. Patients were classified by investigator-defined asthma severity (guided by the 2017 Global Initiative for Asthma) and practice type (primary/specialist care). Multivariable regression models analyzed associations between SABA prescriptions and outcomes. RESULTS: Data from 1778 patients (mean age, 43.7 years) were analyzed. Most patients were female (62.4%) and had moderate-to-severe asthma (63.3%), with 57.1 and 42.9% of patients treated in specialist and primary care, respectively. Asthma was partly controlled/uncontrolled in 66.2% of patients, with 57.9% experiencing ≥1 severe exacerbation in the previous 12 months. Overall, 46.5% of patients were prescribed ≥3 SABA canisters in the preceding 12 months (over-prescription); 26.2% were prescribed ≥10 canisters. SABAs were purchased over-the-counter by 32.6% of patients, of whom 79.3% had received SABA prescriptions; 71.9% and 40.1% for ≥3 and ≥10 canisters, respectively. Higher SABA prescriptions (vs. 1-2 canisters) were associated with increased incidence rate of severe exacerbations and lower odds of having at least partly controlled asthma (except 3-5 canisters). CONCLUSIONS: Findings from this African cohort of the SABINA III study indicate that SABA over-prescription and SABA over-the-counter purchase are common and associated with poor asthma-related outcomes. This highlights the need for healthcare providers/policymakers to align clinical practices with the latest treatment recommendations.

New antituberculous drugs in development.

There have been no new antituberculous drugs since the introduction of rifampin in 1952. The collision of the HIV and tuberculosis (TB) epidemics in developing regions of the world together with the emergence of multidrug resistance and extensively drug-resistant strains of TB has emphasized the urgent need for newer antituberculous drugs. There is a need for drugs that are safe, effective against resistant strains, are able to shorten the course of treatment, are effective for latent TB infection, and that have minimal interactions with antiretroviral drugs. Drugs that are currently in phase 3 development are moxifloxacin and gatifloxacin. In phase 2 development are PA-824 and TMC207; and in phase 1 are SQ109, AZD5847, and linezolid. Nanotechnology holds future promise for targeted drug delivery. Immunotherapy such as new vaccines and vitamin D may serve as adjunctive treatment for prevention and active disease, together with shortening the course of treatment. Bringing newer and more effective antituberculous drugs to market is a global priority and the process must be accelerated.

TRAV1-2+ CD8+ T-cells including oligoconal expansions of MAIT cells are enriched in the airways in human tuberculosis.

Mucosal-associated invariant T (MAIT) cells typically express a TRAV1-2+ semi-invariant TCRα that enables recognition of bacterial, mycobacterial, and fungal riboflavin metabolites presented by MR1. MAIT cells are associated with immune control of bacterial and mycobacterial infections in murine models. Here, we report that a population of pro-inflammatory TRAV1-2+ CD8+ T cells are present in the airways and lungs of healthy individuals and are enriched in bronchoalveolar fluid of patients with active pulmonary tuberculosis (TB). High-throughput T cell receptor analysis reveals oligoclonal expansions of canonical and donor-unique TRAV1-2+ MAIT-consistent TCRα sequences within this population. Some of these cells demonstrate MR1-restricted mycobacterial reactivity and phenotypes suggestive of MAIT cell identity. These findings demonstrate enrichment of TRAV1-2+ CD8+ T cells with MAIT or MAIT-like features in the airways during active TB and suggest a role for these cells in the human pulmonary immune response to Mycobacterium tuberculosis.

Recent advances in the medical and surgical treatment of multi-drug resistant tuberculosis.

PURPOSE OF REVIEW: Multi-drug resistant tuberculosis is a serious clinical problem. Extension of drug resistance to second-line anti-tuberculosis drugs in the form of the W-strain is cause for alarm. There is an urgent need for more rapid recognition of multi-drug resistant tuberculosis and newer therapeutic agents. This review summarizes the recent advances in the diagnosis and treatment of multi-drug resistant tuberculosis including surgery and new developments. RECENT FINDINGS: Multidrug resistant tuberculosis therapy is characterized by prolonged treatment, high morbidity and mortality, and high relapse rates. New diagnostic procedures that include electrophoretic and molecular hybridization techniques will allow rapid diagnosis. Several new drugs are currently in various phases of development. Moxifloxacin, a respiratory fluoroquinolone, is currently in phase III clinical development. New classes of drugs such as nitroimidazopyrans (PA-824) and diarylquinolines (R-207910) are exciting based on phase I and II data. Immunomodulation with vaccines and interferon-gamma have been unhelpful. Surgery is reserved for selected cases only. Cure rates of over 90% with reasonable morbidity and mortality has been achieved with meticulous preoperative preparation, patient selection and careful surgical technique. SUMMARY: Newer drugs and defined indications for surgery should provide improved cure rates, with reduced duration of treatment for multi-drug resistant tuberculosis.