Chronic obstructive pulmonary disease and emerging ER stress-related therapeutic targets.

COPD pathogenesis is frequently associated with endoplasmic reticulum stress (ER stress) progression. Targeting the major unfolded protein response (UPR) branches in the ER stress pathway may provide pharmacotherapeutic selection strategies for treating COPD and enable relief from its symptoms. In this study, we aimed to systematically review the potential role of the ER stress inhibitors of major UPR branches (IRE1, PERK, and ATF6) in COPD-related studies and determine the current stage of knowledge in this field. The systematic review was carried out adhering to the PRISMA checklist based on published studies obtained from specific keyword searches of three databases, namely PubMed, ScienceDirect and Springer Database. The search was limited to the year 2000-2022 which includes all in vitro studies, in vivo studies and clinical trials related to the application of ER stress inhibitors toward COPD-induced models and disease. The risk of bias was evaluated using the QUIN, SYRCLE, revised Cochrane risk of bias tool for randomized trials (RoB 2.0) and NIH tool respectively. A total of 7828 articles were screened from three databases and a final total of 37 studies were included in the review. The ER stress and UPR pathways are potentially useful to prevent COPD progression and attenuate the exacerbation of COPD and related symptoms. Interestingly, the off-target effects from inhibition of the UPR pathway may be desirable or undesirable depending on context and therapeutic applications. Targeting the UPR pathway could have complex consequences as the production of ER molecules involved in folding may be impaired which could continuously provoke misfolding of proteins. Although several emerging compounds were noted to be potentially useful for targeted therapy against COPD, clinical studies have yet to be thoroughly explored.

Osteoporosis among Patients with Chronic Obstructive Pulmonary Disease: Systematic Review and Meta-analysis of Prevalence, Severity, and Therapeutic Outcomes.

Chronic obstructive pulmonary disease (COPD) can be associated with systemic inflammatory trademarks and can coexist with other chronic debilitating diseases such as osteoporosis, which is considered among the most serious comorbidities of COPD. In this review, we aimed at finding answers for the following questions and tried to encapsulate the available literature: (1) how prevalent is osteoporosis among patients with COPD? (2) What are severity patterns of osteoporosis in case of COPD? (3) What are the therapeutic outcomes for patients with osteoporotic COPD? The total number of patients with COPD from all studies was 3815, majority of which were male (2658) representing 69.67% of patients. The mean ± standard deviation for percentage of forced expiratory volume in 1s (FEV1%) was 55.43 ± 14.62%, body mass index for almost 91.29% of patients was 24.4 ± 4.45 kg/m2, whereas fat-free mass index (FFMI) was 17 ± 0.93 kg/m2 for 17.66%. The percentage of patients with COPD having osteoporosis varied in the analyzed studies from 14% up to 66.6%. The mean prevalence of reported osteopenia from 14 studies (n = 2107) was 39.91%, whereas for osteoporosis, the mean prevalence was 37.62% for all included studies. Osteoporosis was highly prevalent among patients with COPD. It is reasonable to call for osteoporosis screening in patients with COPD who are above 65 years, in advanced stages, with BMI lower than 21 kg/m2 or with FFMI lower than 16 kg/m2 for males and 15 kg/m2 for females. There is a lack of research investigating severity and treatments of osteoporosis in patients with COPD.

It is time to change the way we manage mild asthma: an update in GINA 2019.

Asthma is a heterogeneous lung disease, usually characterised by chronic airway inflammation. Although evidence-based treatments are available in most countries, asthma control remains suboptimal, and asthma-related deaths continue to be an ongoing concern. Generally, it is believed that between 50 to 75% of patients with asthma can be considered as having mild asthma.Previous versions of Global Initiative for Asthma (GINA) suggested that mild asthma in adults can be well managed with either reliever medications, for example, short-acting beta2 agonists (SABA) alone or with the additional use of controllers such as regular low-dose inhaled corticosteroids (ICS). Given the low frequency or non-bothersome nature of symptoms in mild asthma, patients' adherence towards their controller medications, especially to ICS is usually not satisfactory. Such patients often rely on SABA alone to relieve symptoms, which may contribute to SABA over-reliance. Overuse of relievers such as SABAs has been associated with poor asthma outcomes, such as exacerbations and even deaths. The new GINA 2019 asthma treatment recommendations represent significant shifts in asthma management at Steps 1 and 2 of the 5 treatment steps. The report acknowledges an emerging body of evidence suggesting the non-safety of SABAs overuse in the absence of concomitant controller medications, therefore does not support SABA-only therapy in mild asthma and has included new off-label recommendations such as symptom-driven (as-needed) low dose ICS-formoterol and "low dose ICS taken whenever SABA is taken".The GINA 2019 report highlights significant updates in mild asthma management and these recommendations represent a clear deviation from decades of clinical practice mandating the use of symptom-driven SABA treatment alone in those with mild asthma. While the new inclusions of strategies such as symptom-driven (as-needed) ICS-formoterol and "ICS taken whenever SABA is taken" are based on several key trials, data in this context are still only emergent data, with clear superiority of as needed ICS-formoterol combinations over maintenance ICS regimens yet to be established for valid endpoints. Nevertheless, current and emerging data position the clinical asthma realm at a watershed moment with imminent changes for the way we manage mild asthma likely in going forward.

Assessing Airflow Limitation among Smokers in a Primary Care Setting.

BACKGROUND: Many smokers have undiagnosed chronic obstructive pulmonary disease (COPD), and yet screening for COPD is not recommended. Smokers who know that they have airflow limitation are more likely to quit smoking. This study aims to identify the prevalence and predictors of airflow limitation among smokers in primary care. METHODS: Current smokers ≥ 40 years old who were asymptomatic clinic attendees in a primary care setting were recruited consecutively for two months. We used a two-step strategy. Step 1: participants filled in a questionnaire. Step 2: Assessment of airflow limitation using a pocket spirometer. Multiple logistic regression was utilised to determine the best risk predictors for airflow limitation. RESULTS: Three hundred participants were recruited. Mean age was 58.35 (SD 10.30) years old and mean smoking history was 34.56 pack-years (SD 25.23). One in two smokers were found to have airflow limitation; the predictors were Indian ethnicity, prolonged smoking pack-year history and Lung Function Questionnaire score ≤ 18. Readiness to quit smoking and the awareness of COPD were low. CONCLUSIONS: The high prevalence of airflow limitation and low readiness to quit smoking imply urgency with helping smokers to quit smoking. Identifying airflow limitation as an additional motivator for smoking cessation intervention may be considered. A two-step case-finding method is potentially feasible.

Evaluation of Adverse Reactions Induced by Anti-Tuberculosis Drugs in Hospital Pulau Pinang.

BACKGROUND: The use of multi-drug regimens in tuberculosis (TB) treatment has been associated with undesirable adverse drug reactions (ADRs). This study aims to assess the incidence and impact of ADRs on TB treatment in Hospital Pulau Pinang. METHODS: This cross-sectional study was conducted via retrospective review of outpatients' medical records. Details regarding ADRs were identified by a pharmacist and verified by a consultant respiratory physician. RESULTS: A total of 91 cases, out of 210 patients enrolled in this study, were detected with 75 patients (35.7%) experienced at least one ADR. The three most common ADRs detected were cutaneous adverse drug reactions (CADRs) (21.0%), drug-induced hepatitis (DIH) (7.1%) and gastrointestinal disturbance (4.8%). Pyrazinamide was the most common causative agent and 15.7% of all TB patients required treatment modification due to ADRs. Females were shown to have a higher tendency to develop ADRs than the males in this study (P = 0.009). The development of ADRs was shown not to affect the TB treatment outcomes (P = 0.955). CONCLUSION: The incidence of ADRs in this study was high so it is important to identify the risk factors for ADRs and the individuals who have those risk factors when initiating anti-TB drugs. These individuals require special attention when anti-TB drugs are initiated.