Exploring the perceptions of patients with chronic respiratory diseases and their insights into pulmonary rehabilitation in Bangladesh.

Background: Chronic respiratory diseases (CRDs) require holistic management which considers patients' preferences, appropriate pharmacotherapy, pulmonary rehabilitation, and integrated care. We aimed to understand the perceptions of people with CRDs about their condition and pulmonary rehabilitation in Bangladesh. Methods: We conducted semi-structured interviews with a maximum variation sample of people with CRDs who had participated in a feasibility study of pulmonary rehabilitation in 2021/2022. A multidisciplinary team transcribed the interviews verbatim and analysed them in Bengali using a grounded theory approach. Results: We interviewed 15 participants with chronic obstructive pulmonary disease, asthma, or post-tuberculosis. The analysis revealed three themes. The first encompassed understanding CRDs: Patients characterised their condition by the symptoms (e.g. 'Hapani' meaning 'breathlessness') rather than describing a disease entity. Some believed occupation, previous infection, or family history to be a cause. The second theme included perceptions of pulmonary rehabilitation: Exercise was counterintuitive, as it exacerbated the breathlessness symptom that defined their disease. Views varied, though many acknowledged the benefits after a few sessions. Even with home-based programmes, participants described practical barriers to finding time for the sessions and adopted strategies to overcome the challenges. The third theme focused on implementation: Participants highlighted the need for raising awareness of CRDs and the potential of pulmonary rehabilitation in the community, adapting to the local context, and establishing an accessible resourced service. Conclusions: Understanding how patients and their communities perceive their condition and the barriers (both conceptual and logistical) to acceptance is the first step to embedding this highly effective intervention into routine health care services in Bangladesh with potential benefits for the increasing number of people living with CRDs in low- and middle-income countries.

Developing a home-based pulmonary rehabilitation programme for patients with chronic respiratory diseases in Malaysia: A mixed-method feasibility study.

Background: The COVID-19 pandemic has underscored the importance of remote healthcare and home-based interventions, including pulmonary rehabilitation, for patients with chronic respiratory diseases (CRDs). It has also heightened the vulnerability of individuals with underlying respiratory conditions to severe illness from COVID-19, necessitating exploration and assessment of the feasibility of delivering home - pulmonary rehabilitation (home-PR) programmes for CRD management in Malaysia and other countries. Home-based programmes offer a safer alternative to in-person rehabilitation during outbreaks like COVID-19 and can serve as a valuable resource for patients who may be hesitant to visit healthcare facilities during such times. We aimed to assess the feasibility of delivering a home-PR programme for patients with CRDs in Malaysia. Methods: We recruited patients with CRDs from two hospitals in Klang Valley, Malaysia to a home-PR programme. Following centre-based assessment, patients performed the exercises at home (five sessions/week for eight weeks (total 40 sessions)). We monitored the patients via weekly telephone calls and asked about adherence to the programme. We measured functional exercise capacity (6-Minutes Walking Test (6MWT) and Health-Related Quality-of-Life (HRQoL) (COPD Assessment Test (CAT)) at baseline and post-PR at nine weeks. We conducted semi-structured interviews with 12 purposively sampled participants to explore views and feedback on the home-PR programme. The interviews were audio recorded, transcribed verbatim, and analysed thematically. Results: We included 30 participants; two withdrew due to hospitalisation. Although 28 (93%) adhered to the full programme, only 11 (37%) attended the post-PR assessment because COVID-19 movement restrictions in Malaysia at that time prevented attendance at the centre. Four themes emerged from the qualitative analysis: involvement of family and caregivers, barriers to home-PR programme, interactions with peers and health care professionals, and programme enhancement. Conclusion: Despite the COVID-19 pandemic, the home-PR programme proved feasible for remote delivery, although centre-based post-PR assessments were not possible. Family involvement played an important role in the home-PR programme. The delivery of this programme can be further improved to maximise the benefit for patients.

Asynchronous digital health interventions for reviewing asthma: A mixed-methods systematic review protocol.

INTRODUCTION: People living with asthma require regular reviews to address their concerns and questions, assess control, review medication, and support self-management. However, practical barriers to attending face-to-face consultations might limit routine reviews. Reviewing asthma using asynchronous digital health interventions could be convenient for patients and an efficient way of maintaining communication between patients and healthcare professionals and improving health outcomes. We, therefore, aim to conduct a mixed-methods systematic review to assess the effectiveness of reviewing asthma by asynchronous digital health interventions and explore the views of patients and healthcare professionals about the role of such interventions in delivering asthma care. METHODS: We will search MEDLINE, Embase, Scopus, PsycInfo, CINAHL, and Cochrane Library from 2001 to present without imposing any language restrictions. We are interested in studies of asynchronous digital health interventions used either as a single intervention or contributing to mixed modes of review. Two review authors will independently screen titles and abstracts, and retrieve potentially relevant studies for full assessment against the eligibility criteria and extract data. Disagreements will be resolved by discussion with the review team. We will use 'Downs and Black' checklist, 'Critical Appraisal Skills Programme', and 'Mixed Methods Appraisal Tool' to assess methodological quality of quantitative, qualitative, and mixed-methods studies respectively. After synthesising quantitative (narrative synthesis) and qualitative (thematic synthesis) data separately, we will integrate them following methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions. CONCLUSION: The findings of this review will provide insights into the role of asynchronous digital health interventions in the routine care of people living with asthma. TRIAL REGISTRATION: Systematic review registration: PROSPERO registration number: CRD42022344224.

Mapping national information and communication technology (ICT) infrastructure to the requirements of potential digital health interventions in low- and middle-income countries.

Background: Digital health can support health care in low- and middle-income countries (LMICs) by overcoming problems of distance, poor infrastructure and the need to provide community practitioners with specialist support. We used five RESPIRE countries as exemplars (Bangladesh, India, Indonesia, Malaysia, Pakistan) to identify the digital health solutions that are valuable in their local setting, worked together with local clinicians and researchers to explore digital health policy, electricity/ICT infrastructure, and socio-cultural factors influencing users' ability to access, adopt and utilise digital health. Methods: We adopted the Joanna Briggs Institute's scoping review protocol and followed the Cochrane Rapid Review method to accelerate the review process, using the Implementation and Operation of Mobile Health projects framework and The Extended Technology Acceptance Model of Mobile Telephony to categorise the results. We conducted the review in four stages: (1) establishing value, (2) identifying digital health policy, (3) searching for evidence of infrastructure, design, and end-user adoption, (4) local input to interpret relevance and adoption factors. We used open-source national/international statistics such as the World Health Organization, International Telecommunication Union, Groupe Speciale Mobile, and local news/articles/government statistics to scope the current status, and systematically searched five databases for locally relevant exemplars. Results: We found 118 studies (2015-2021) and 114 supplementary online news articles and national statistics. Digital health policy was available in all countries, but scarce skilled labour, lack of legislation/interoperability support, and interrupted electricity and internet services were limitations. Older patients, women and those living in rural areas were least likely to have access to ICT infrastructure. Renewable energy has potential in enabling digital health care. Low usage mobile data and voice service packages are relatively affordable options for mHealth in the five countries. Conclusions: Effective implementation of digital health technologies requires a supportive policy, stable electricity infrastructures, affordable mobile internet service, and good understanding of the socio-economic context in order to tailor the intervention such that it functional, accessible, feasible, user-friendly and trusted by the target users. We suggest a checklist of contextual factors that developers of digital health initiatives in LMICs should consider at an early stage in the development process.

Effectiveness of home-based pulmonary rehabilitation: systematic review and meta-analysis.

INTRODUCTION: Despite proven effectiveness for people with chronic respiratory diseases, practical barriers to attending centre-based pulmonary rehabilitation (centre-PR) limit accessibility. We aimed to review the clinical effectiveness, components and completion rates of home-based pulmonary rehabilitation (home-PR) compared to centre-PR or usual care. METHODS AND ANALYSIS: Using Cochrane methodology, we searched (January 1990 to August 2021) six electronic databases using a PICOS (population, intervention, comparison, outcome, study type) search strategy, assessed Cochrane risk of bias, performed meta-analysis and narrative synthesis to answer our objectives and used the Grading of Recommendations, Assessment, Development and Evaluations framework to rate certainty of evidence. RESULTS: We identified 16 studies (1800 COPD patients; 11 countries). The effects of home-PR on exercise capacity and/or health-related quality of life (HRQoL) were compared to either centre-PR (n=7) or usual care (n=8); one study used both comparators. Compared to usual care, home-PR significantly improved exercise capacity (standardised mean difference (SMD) 0.88, 95% CI 0.32-1.44; p=0.002) and HRQoL (SMD -0.62, 95% CI -0.88--0.36; p<0.001). Compared to centre-PR, home-PR showed no significant difference in exercise capacity (SMD -0.10, 95% CI -0.25-0.05; p=0.21) or HRQoL (SMD 0.01, 95% CI -0.15-0.17; p=0.87). CONCLUSION: Home-PR is as effective as centre-PR in improving functional exercise capacity and quality of life compared to usual care, and is an option to enable access to pulmonary rehabilitation.

Clinical effectiveness and components of Home-pulmonary rehabilitation for people with chronic respiratory diseases: a systematic review protocol.

INTRODUCTION: Chronic respiratory diseases (CRDs) are common and disabling conditions that can result in social isolation and economic hardship for patients and their families. Pulmonary rehabilitation (PR) improves functional exercise capacity and health-related quality of life (HRQoL) but practical barriers to attending centre-based sessions or the need for infection control limits accessibility. Home-PR offers a potential solution that may improve access. We aim to systematically review the clinical effectiveness, completion rates and components of Home-PR for people with CRDs compared with Centre-PR or Usual care. METHODS AND ANALYSIS: We will search PubMed, CINAHL, Cochrane, EMBASE, PeDRO and PsycInfo from January 1990 to date using a PICOS search strategy (Population: adults with CRDs; Intervention: Home-PR; Comparator: Centre-PR/Usual care; Outcomes: functional exercise capacity and HRQoL; Setting: any setting). The strategy is to search for 'Chronic Respiratory Disease' AND 'Pulmonary Rehabilitation' AND 'Home-PR', and identify relevant randomised controlled trials and controlled clinical trials. Six reviewers working in pairs will independently screen articles for eligibility and extract data from those fulfilling the inclusion criteria. We will use the Cochrane risk-of-bias tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the quality of evidence. We will perform meta-analysis or narrative synthesis as appropriate to answer our three research questions: (1) what is the effectiveness of Home-PR compared with Centre-PR or Usual care? (2) what components are used in effective Home-PR studies? and (3) what is the completion rate of Home-PR compared with Centre-PR? ETHICS AND DISSEMINATION: Research ethics approval is not required since the study will review only published data. The findings will be disseminated through publication in a peer-reviewed journal and presentation in conferences. PROSPERO REGISTRATION NUMBER: CRD42020220137.

Systematic review of clinical effectiveness, components, and delivery of pulmonary rehabilitation in low-resource settings.

Pulmonary rehabilitation (PR) is a guideline-recommended multifaceted intervention that improves the physical and psychological well-being of people with chronic respiratory diseases (CRDs), though most of the evidence derives from trials in high-resource settings. In low- and middle-income countries, PR services are under-provided. We aimed to review the effectiveness, components and mode of delivery of PR in low-resource settings. Following Cochrane methodology, we systematically searched (1990 to October 2018; pre-publication update March 2020) MEDLINE, EMBASE, CABI, AMED, PUBMED, and CENTRAL for controlled clinical trials of adults with CRD (including but not restricted to chronic obstructive pulmonary disease) comparing PR with usual care in low-resource settings. After duplicate selection, we extracted data on exercise tolerance, health-related quality of life (HRQoL), breathlessness, included components, and mode of delivery. We used Cochrane risk of bias (RoB) to assess study quality and synthesised data narratively. From 8912 hits, we included 13 studies: 11 were at high RoB; 2 at moderate RoB. PR improved functional exercise capacity in 10 studies, HRQoL in 12, and breathlessness in 9 studies. One of the two studies at moderate RoB showed no benefit. All programmes included exercise training; most provided education, chest physiotherapy, and breathing exercises. Low cost services, adapted to the setting, used limited equipment and typically combined outpatient/centre delivery with a home/community-based service. Multicomponent PR programmes can be delivered in low-resource settings, employing a range of modes of delivery. There is a need for a high-quality trial to confirm the positive findings of these high/moderate RoB studies.

Continuing professional education for general practitioners on chronic obstructive pulmonary disease: feasibility of a blended learning approach in Bangladesh.

BACKGROUND: Continuing medical education (CME) is essential to developing and maintaining high quality primary care. Traditionally, CME is delivered face-to-face, but due to geographical distances, and pressure of work in Bangladesh, general practitioners (GPs) are unable to relocate for several days to attend training. Using chronic obstructive pulmonary disease (COPD) as an exemplar, we aimed to assess the feasibility of blended learning (combination of face-to-face and online) for GPs, and explore trainees' and trainers' perspectives towards the blended learning approach. METHODS: We used a mixed-methods design. We trained 49 GPs in two groups via blended (n = 25) and traditional face-to-face approach (n = 24) and assessed their post-course knowledge and skills. The COPD Physician Practice Assessment Questionnaire (COPD-PPAQ) was administered before and one-month post-course. Verbatim transcriptions of focus group discussions with 18 course attendees and interviews with three course trainers were translated into English and analysed thematically. RESULTS: Forty GPs completed the course (Blended: 19; Traditional: 21). The knowledge and skills post course, and the improvement in self-reported adherence to COPD guidelines was similar in both groups. Most participants preferred blended learning as it was more convenient than taking time out of their busy work life, and for many the online learning optimised the benefits of the subsequent face-to-face sessions. Suggested improvements included online interactivity with tutors, improved user friendliness of the e-learning platform, and timing face-to-face classes over weekends to avoid time-out of practice. CONCLUSIONS: Quality improvement requires a multifaceted approach, but adequate knowledge and skills are core components. Blended learning is feasible and, with a few caveats, is an acceptable option to GPs in Bangladesh. This is timely, given that online learning with limited face-to-face contact is likely to become the norm in the on-going COVID-19 pandemic.

Systematic review (protocol) of clinical effectiveness and models of care of low-resource pulmonary rehabilitation.

More than half of the people with chronic respiratory diseases (CRDs) live in low- and middle-income countries (LMICs). The increasing disability, reduced productivity, associated anxiety and depression from CRDs result in social isolation and economic hardship for patients and their families. Pulmonary rehabilitation (PR) is a guideline-recommended multidisciplinary and multifaceted intervention that improves the physical and psychological condition of people with CRD. However, PR services are underprovided and uptake is poor in LMICs, especially in low-resourced setting. We aim to systematically assess the effectiveness, applicable components and mode of delivery of PR. We will search MEDLINE, EMBASE, CABI, AMED and CENTRAL from January 1990 using a PICOS search strategy (Population: adults with CRD (including chronic obstructive pulmonary disease, post-tuberculosis, remodelled asthma); Intervention: PR; Comparator: usual care; Outcomes: functional exercise capacity and Health-Related Quality-of-Life; Setting: low-resource settings). Two reviewers will independently screen titles/abstracts and full texts for eligibility and extract data from included papers. We will use the Cochrane Risk-of-Bias tool, rating the quality of evidence using GRADE. We will use narrative synthesis to answer our three objectives: What is the effectiveness of PR in low-resource settings? What components are used in effective studies? What models of service delivery are used? This systematic review will inform the potential impact and practical models of low-resource PR for the betterment of patients with CRDs to improve their substantial health-care burden and address poor quality of life.

Incidence of pulmonary tuberculosis in garments workers of Dhaka City, Bangladesh.

This study was conducted to find out the incidence of Pulmonary Tuberculosis (PT) in garments workers of Dhaka city and to find-out the relationship between the incidence of PT and socio-demographic factors of the respondents. From all garments factories of Dhaka city, 30 factories were included by stratified random sampling method. Then workers were selected by simple random sampling technique. Following selection, detailed history was taken and recorded in a pre-tested questionnaire. Chest X-ray, Sputum for AFB, M.T and ESR were done in the suspected cases. PT was diagnosed when any patient fulfilled predefined inclusion criteria. Out of 2400 selected workers, 2281 workers were studied finally. A total of 22 (9.6 per 1000) definite PT cases were identified. Sputum positive were 4/2281 (1.75 per 1000) cases. All were diagnosed as new cases; none had received any treatment of tuberculosis in the past. The study concludes that PT among the garments workers is a more alarming health issue than among the general population of Bangladesh. Improved and regular health check-up system and 'directly observed treatment shortcourse' (DOTS) should be implemented in the working places particularly where clusters of workers are working together.

Disruption of gamma-glutamyl leukotrienase results in disruption of leukotriene D(4) synthesis in vivo and attenuation of the acute inflammatory response.

To study the function of gamma-glutamyl leukotrienase (GGL), a newly identified member of the gamma-glutamyl transpeptidase (GGT) family, we generated null mutations in GGL (GGL(tm1)) and in both GGL and GGT (GGL(tm1)-GGT(tm1)) by a serial targeting strategy using embryonic stem cells. Mice homozygous for GGL(tm1) show no obvious phenotypic changes. Mice deficient in both GGT and GGL have a phenotype similar to the GGT-deficient mice, but approximately 70% of these mice die before 4 weeks of age, at least 2 months earlier than mice deficient only in GGT. These double-mutant mice are unable to cleave leukotriene C(4) (LTC(4)) to LTD(4), indicating that this conversion is completely dependent on the two enzymes, and in some organs (spleen and uterus) deletion of GGL alone abolished more than 90% of this activity. In an experimental model of peritonitis, GGL alone is responsible for the generation of peritoneal LTD(4). Further, during the development of peritonitis, GGL-deficient mice show an attenuation in neutrophil recruitment but not of plasma protein influx. These findings demonstrate an important role for GGL in the inflammatory response and suggest that LTC(4) and LTD(4) have distinctly different functions in the inflammatory process.

Altered gene expression in the liver of gamma-glutamyl transpeptidase-deficient mice.

We used mice deficient in gamma-glutamyl transpeptidase (GGT) to analyze the effects of GGT deficiency and altered thiol levels on gene expression in liver. GGT-deficient mice have markedly reduced levels of glutathione (GSH), cysteine, methionine, and cysteinylglycine in liver. Steady-state RNA levels of the catalytic subunit of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme in GSH synthesis, are elevated 4-fold in these mice, while those for glutathione synthetase (GSH syn) are elevated 2-fold. RNA levels of cystathionase (cystathionine gamma-lyase), a key enzyme in the synthesis of cysteine from methionine, are elevated approximately 3.5-fold. In contrast, levels of RNA coding for multidrug resistance protein 2 (MRP2), which transports GSH into bile, are half wild-type values. We found no change in RNA levels of enzymes related to oxidative injury (CuZn and Mn superoxide dismutases [SOD], catalase, and glutathione peroxidase). Similarly, RNA levels of glutathione reductase and ribonucleotide reductase were unchanged. Furthermore, in contrast to previous in vitro results, methyl methanesulfonate did not induce stress-activated signal transduction as measured by c-jun phosphorylation in livers of GGT-deficient mice, despite further depletion of GSH by buthionine sulfoximine. Our findings indicate that GGT deficiency itself and/or altered thiol levels regulate expression of genes involved in GSH metabolism, but have no effect on the expression of other antioxidant genes.

Glutathione synthesis is essential for mouse development but not for cell growth in culture.

Glutathione (GSH) is a major source of reducing equivalents in mammalian cells. To examine the role of GSH synthesis in development and cell growth, we generated mice deficient in GSH by a targeted disruption of the heavy subunit of gamma-glutamylcysteine synthetase (gammaGCS-HS(tm1)), an essential enzyme in GSH synthesis. Embryos homozygous for gammaGCS-HS(tm1) fail to gastrulate, do not form mesoderm, develop distal apoptosis, and die before day 8.5. Lethality results from apoptotic cell death rather than reduced cell proliferation. We also isolated cell lines from homozygous mutant blastocysts in medium containing GSH. These cells also grow indefinitely in GSH-free medium supplemented with N-acetylcysteine and have undetectable levels of GSH; further, they show no changes in mitochondrial morphology as judged by electron microscopy. These data demonstrate that GSH is required for mammalian development but dispensable in cell culture and that the functions of GSH, not GSH itself, are essential for cell growth.

Mouse leukotriene A4 hydrolase is expressed at high levels in intestinal crypt cells and splenic lymphocytes.

LTA4 hydrolase (EC 3.3.2.6) is a dual-function enzyme that is essential for the conversion of leukotriene A4 (LTA4) to leukotriene B4 (LTB4) and also possesses an aminopeptidase activity. To characterize the expression of this unusual enzyme, we have cloned the mouse LTA4 hydrolase cDNA. The deduced amino acid sequence revealed 92% identity with the human sequence. Cloning and analysis of genomic sequences of mouse LTA4 hydrolase indicated that it is a single-copy gene spanning over 40kb and containing 20 exons. LTA4 hydrolase is widely expressed, with the highest levels of expression occurring in the small intestine, followed by the spleen. In situ hybridization revealed that LTA4 hydrolase is localized in the crypt cells of the small intestine, white pulp of the spleen, bronchiolar epithelium of the lung, myocardium, adrenal cortex, epithelium of the seminal vesicles, proximal tubules and the collecting ducts of the kidney, and occasional hepatocytes. Thus the widespread distribution of LTA4 hydrolase in various cell types in the tissues suggests that LTB4 may possess biological activities other than those known at present. It is also plausible that the widespread occurrence of LTA4 hydrolase in various tissues may correspond more with its function as an aminopeptidase than its function as an LTA4 hydrolase.

Leukotriene D4 and cystinyl-bis-glycine metabolism in membrane-bound dipeptidase-deficient mice.

We have developed mice deficient in membrane-bound dipeptidase (MBD, EC 3.4.13.19), the enzyme believed to be responsible for the conversion of leukotriene D4 (LTD4) to leukotriene E4 (LTE4). The MBD mutation generated by us was demonstrated to be a null mutation by Northern blot analysis and the absence of beta-lactamase activity in lung, kidney, small intestine, and heart. MBD gene deletion had no effect on viability or fertility. The mutant mice retain partial ability to convert LTD4 to LTE4, ranging from 80-90% of the wild-type values in small intestine and liver to 16% in kidney and 40% in lung, heart, and pancreas. MBD is also believed to function consecutively after gamma-glutamyl transpeptidase to cleave cystinyl-bis-glycine (cys-bis-gly) generated from glutathione cleavage. Our data indicate that kidney homogenates from MBD-deficient mice retain approximately 40% of their ability to cleave cys-bis-gly, consistent with only modest elevations (3-5-fold) of cys-bis-gly in urine from MBD-deficient mice. These observations demonstrate that the conversion of LTD4 to LTE4 and the degradation of cys-bis-gly are catalyzed by at least two alternative pathways (one of which is MBD) that complement each other to varying extents in different tissues.