Lower airway colonization and inflammatory response in COPD: a focus on Haemophilus influenzae

Bacterial infection of the lower respiratory tract in chronic obstructive pulmonary disease (COPD) patients is common both in stable patients and during acute exacerbations. The most frequent bacteria detected in COPD patients is Haemophilus influenzae, and it appears this organism is uniquely adapted to exploit immune deficiencies associated with COPD and to establish persistent infection in the lower respiratory tract. The presence of bacteria in the lower respiratory tract in stable COPD is termed colonization; however, there is increasing evidence that this is not an innocuous phenomenon but is associated with airway inflammation, increased symptoms, and increased risk for exacerbations. In this review, we discuss host immunity that offers protection against H. influenzae and how disturbance of these mechanisms, combined with pathogen mechanisms of immune evasion, promote persistence of H. influenzae in the lower airways in COPD. In addition, we examine the role of H. influenzae in COPD exacerbations, as well as interactions between H. influenzae and respiratory virus infections, and review the role of treatments and their effect on COPD outcomes. This review focuses predominantly on data derived from human studies but will refer to animal studies where they contribute to understanding the disease in humans

“I wouldn't survive it, as simple as that”: Syndemic vulnerability among people living with chronic non-communicable disease during the COVID-19 pandemic

The co-occurrence of COVID-19, non-communicable diseases and socioeconomic disadvantage has been identified as creating a syndemic: a state of synergistic epidemics, occurring when co-occurring health conditions interact with social conditions to amplify the burden of disease. In this study, we use the concept of illness management work to explore the impact of the COVID-19 pandemic on the lives of people living with, often multiple, chronic health conditions in a range of social circumstances. In-depth interviews were conducted between May and July 2020 with 29 participants living in a city in North East England. Qualitative data provide unique insights for those seeking to better understand the consequences for human life and wellbeing of the interacting social, physical and psychological factors that create syndemic risks in people's lives. Among this group of people at increased vulnerability to harm from COVID-19, we find that the pandemic public health response increased the work required for condition management. Mental distress was amplified by fear of infection and by the requirements of social isolation and distancing that removed participants' usual sources of support. Social conditions, such as poor housing, low incomes and the requirement to earn a living, further amplified the work of managing everyday life and risked worsening existing mental ill health. As evidenced by the experiences reported here, the era of pandemics will require a renewed focus on the connection between health and social justice if stubborn, and worsening health and social inequalities are to be addressed or, at the very least, not increased

"We can't carry the weight of the whole world": illness experiences among Peruvian older adults with symptoms of depression and anxiety

Background: Despite the high levels of depression and anxiety symptoms in old age, the use of mental health services in this population is low. Help-seeking behaviors are shaped by how an individual perceives and experiences their illness. The objective of this study was to characterize the illness experiences of Peruvian older adults with depression and anxiety symptoms in order to lay the foundation for tailored community-based mental health interventions. Methods: In this qualitative study, we conducted in-depth interviews with a purposively selected sample of older adults (≥ 60 years) from peri-urban areas of Lima, Peru. We included individuals with only depressive symptoms (Patient Health Questionnaire-9 ≥ 10), only anxiety symptoms (Beck Anxiety Inventory ≥ 16), with depressive and anxiety symptoms, and older adults who mentioned they had received mental health treatment/care. The interview guide included the following topics: perceptions and experiences about depression and anxiety; perceptions about the relationship between physical chronic diseases and mental health; experiences with mental health professionals and treatments, and coping mechanisms. Data collection was conducted between October 2018 and February 2019. Results: We interviewed 38 participants (23 women, 15 men) with a mean age of 67.9 years. Participants' ideas and perceptions of depression and anxiety showed considerable overlap. Participants attributed depression and anxiety mainly to familial and financial problems, loneliness, loss of independence and past traumatic experiences. Coping strategies used by older adults included 'self-reflection and adaptation' to circumstances, 'do your part', and seeking 'emotional support' mainly from non-professionals (relatives, friends, acquaintances, and religion). Conclusions: Illness experiences of depression and anxiety set the pathway for tailored community-based mental health interventions for older adults. Overlapping narratives and perceptions of depression and anxiety suggest that these conditions should be addressed together. Mental health interventions should incorporate addressing areas related to depression and anxiety such as prevention of loss of independence, trauma, and loneliness. Good acceptability of receiving emotional support for non-professionals might offer an opportunity to incorporate them when delivering mental health care to older adults

Development and Validity Assessment of a Chronic Obstructive Pulmonary Disease Knowledge Questionnaire in Low- and Middle-Income Countries

Rationale: The majority of the morbidity and mortality related to chronic obstructive pulmonary disease (COPD) occurs in low- and middle-income countries (LMICs). Despite the increasing burden of COPD, disease-specific knowledge among healthcare workers (HCWs) and patients in LMICs remains limited. COPD knowledge questionnaires are valid and reliable tools to assess COPD knowledge and can be employed in settings with limited health literacy. Objective: To develop and assess validity and reliability of a COPD knowledge questionnaire among individuals with COPD in three LMIC settings. Methods: Twelve questions were generated by an expert team of sixteen researchers, physicians, and public health professionals to create an LMIC-specific COPD knowledge questionnaire. Content was based on previous instruments, clinical guidelines, focus group discussions, and questionnaire piloting. Participants with COPD completed the questionnaire across three diverse LMIC settings before and three months after delivery of a standardized COPD specific education package by a local community health worker (CHW) trained to deliver the education to an appropriate standard. We utilized paired t-tests to assess improvement in knowledge post-intervention. Results: Questionnaire development initially yielded 52 items. Based on community feedback and expertise, items were eliminated and added yielding a final 12-item questionnaire, with a maximum total score of 12. A total of 196 participants with COPD were included this study in Nepal (n=86), Peru (n=35) and Uganda (n=75). Mean (± SD) baseline score was 8.0 ± 2.5 and 3-months post-education the mean score was 10.2 ± 1.7 among participants. The CHW-led COPD educational intervention improved COPD knowledge among community members by 2.2 points (95% CI 1.8 to 2.6, t=10.9, p<0.001). Internal consistency using Cronbach’s alpha was 0.75. Conclusion: The LMIC COPD-KQ demonstrates face and content validity and acceptable internal consistency through development phases, suggesting a reliable and valid COPD education instrument that can be utilized to assess educational interventions across LMIC settings. Clinical trial registered with ClinicalTrials.gov (NCT03365713

Sarcopenia and sarcopenic obesity among community-dwelling Peruvian adults: A cross-sectional study

Copyright: \ua9 2024 Flores-Flores et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction Sarcopenia and sarcopenic obesity (SO) have emerged as significant contributors to negative health outcomes in the past decade. We aimed to estimate the prevalence of probable sarcopenia, sarcopenia, and SO in a community-dwelling population of 1151 adults aged ≥55 years in Lima, Peru. Methods This cross-sectional study was conducted between 2018 and 2020. Sarcopenia was defined as the presence of low muscle strength (LMS) and low muscle mass (LMM) according to European (EWGSOP2), US (FNIH) and Asian (AWGS2) guidelines. We measured muscle strength by maximum handgrip strength and muscle mass using bioelectrical impedance analyzer. SO was defined as a body mass index ≥ 30 kg/m2 and sarcopenia. Results The study participants had a mean age of 66.2 years (SD 7.1), age range between 60 to 92 years old, of which 621 (53.9%) were men. Among the sample, 41.7% were classified as obese (BMI ≥30.0 kg/m2). The prevalence of probable sarcopenia was estimated to be 22.7% (95%CI: 20.3-25.1) using the EWGSOP2 criteria and 27.8% (95%CI: 25.2-30.4) using the AWGS2 criteria. Sarcopenia prevalence, assessed using skeletal muscle index (SMI), was 5.7% (95%CI: 4.4-7.1) according to EWGSOP2 and 8.3% (95%CI: 6.7-9.9) using AWGS2 criteria. The prevalence of sarcopenia based on the FNIH criteria was 18.1% (95%CI: 15.8-20.3). The prevalence of SO, considering different sarcopenia definitions, ranged from 0.8% (95%CI: 0.3-1.3) to 5.0% (95%CI: 3.8-6.3). Conclusion Our findings reveal substantial variation in the prevalence of sarcopenia and SO, underscoring the necessity for context-specific cut-off values. Although the prevalence of SO was relatively low, this result may be underestimated. Furthermore, the consistently high proportion of probable sarcopenia and sarcopenia point to a substantial public health burden

A Novel Case-Finding Instrument for Chronic Obstructive Pulmonary Disease in Low- and Middle-Income Country Settings

Background: Low- and middle-income countries (LMICs) account for >90% of deaths and illness episodes related to COPD; however, this condition is commonly underdiagnosed in these settings. Case-finding instruments for COPD may improve diagnosis and identify individuals that need treatment, but few have been validated in resource-limited settings. Methods: We conducted a population-based cross-sectional study in Uganda to assess the diagnostic accuracy of a respiratory symptom, exposure and functional questionnaire in combination with peak expiratory flow for COPD diagnosis using post-bronchodilator FEV1/FVC z-score below the 5th percentile as the gold standard. We included locally relevant exposure questions and statistical learning techniques to identify the most important risk factors for COPD. We used 80% of the data to develop the case-finding instrument and validated it in the remaining 20%. We evaluated for calibration and discrimination using standard approaches. The final score, COLA (COPD in LMICs Assessment), included seven questions, age and pre-bronchodilator peak expiratory flow. Results: We analyzed data from 1,173 participants (average age 47 years, 46.9% male, 4.5% with COPD) with acceptable and reproducible spirometry. The seven questions yielded a cross-validated area-under-the-curve [AUC] of 0.68 (95% CI 0.61–0.75) with higher scores conferring greater odds of COPD. The inclusion of peak expiratory flow and age improved prediction in a validation sample (AUC=0.83, 95% CI 0.78–0.88) with a positive predictive value of 50% and a negative predictive value of 96%. The final instrument (COLA) included seven questions, age and pre-bronchodilator peak expiratory flow. Conclusion: COLA predicted COPD in urban and rural settings in Uganda has high calibration and discrimination, and could serve as a simple, low-cost screening tool in resource-limited settings

Effect of Temperature and Heat Treatment on Crack Growth Acoustic Emission in 7075 Aluminum

The acoustic emission activity due to crack advance in 7075 aluminum alloys has been found to vary with both temperature and heat treatment. An Increase in temperature or overaging of material in the -T6 condition each reduces the acoustic emission activity by changing the probability of occurrence of acoustic emission events and lowering their amplitudes. These observations suggest that the acoustic emission source mechanism is not inclusion fracture but rather is a property of the ductile matrix

Quadratic optimal functional quantization of stochastic processes and numerical applications

In this paper, we present an overview of the recent developments of functional quantization of stochastic processes, with an emphasis on the quadratic case. Functional quantization is a way to approximate a process, viewed as a Hilbert-valued random variable, using a nearest neighbour projection on a finite codebook. A special emphasis is made on the computational aspects and the numerical applications, in particular the pricing of some path-dependent European options.Comment: 41 page

Effectiveness of low-dose theophylline for the management of biomass-associated COPD (LODOT-BCOPD): study protocol for a randomized controlled trial

BACKGROUND: COPD is a leading cause of death globally, with the majority of morbidity and mortality occurring in low- and middle-income country (LMIC) settings. While tobacco-smoke exposure is the most important risk factor for COPD in high-income settings, household air pollution from biomass smoke combustion is a leading risk factor for COPD in LMICs. Despite the high burden of biomass smoke-related COPD, few studies have evaluated the efficacy of pharmacotherapy in this context. Currently recommended inhaler-based therapy for COPD is neither available nor affordable in most resource-limited settings. Low-dose theophylline is an oral, once-a-day therapy, long used in high-income countries (HICs), which has been proposed for the management of COPD in LMICs in the absence of inhaled steroids and/or bronchodilators. The Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD) trial investigates the clinical efficacy and cost-effectiveness of low-dose theophylline for the management of biomass-related COPD in a low-income setting. METHODS: LODOT-BCOPD is a randomized, double-blind, placebo-controlled trial to test the efficacy of low-dose theophylline in improving respiratory symptoms in 110 participants with moderate to severe COPD in Central Uganda. The inclusion criteria are as follows: (1) age 40 to 80 years, (2) full-time resident of the study area, (3) daily biomass exposure, (4) post-bronchodilator FEV1/FVC below the 5th percentile of the Global Lung Initiative mixed ethnic reference population, and (5) GOLD Grade B-D COPD. Participants will be randomly assigned to receive once daily low-dose theophylline (200 mg ER, Unicontin-E) or placebo for 52 weeks. All participants will receive education about self-management of COPD and rescue salbutamol inhalers. We will measure health status using the St. George's Respiratory Questionnaire (SGRQ) and quality of life using the EuroQol-5D (EQ-5D) at baseline and every 6 months. In addition, we will assess household air pollution levels, serum inflammatory biomarkers (fibrinogen, hs-CRP), and theophylline levels at baseline, 1 month, and 6 months. The primary outcome is change in SGRQ score at 12 months. Lastly, we will assess the cost-effectiveness of the intervention by calculating quality-adjusted life years (QALYs) from the EQ-5D. TRIAL REGISTRATION: ClinicalTrials.gov  NCT03984188 . Registered on June 12, 2019 TRIAL ACRONYM: Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD)

Stresses and strains on the human fetal skeleton during development

Mechanical forces generated by fetal kicks and movements result in stimulation of the fetal skeleton in the form of stress and strain. This stimulation is known to be critical for prenatal musculoskeletal development; indeed, abnormal or absent movements have been implicated in multiple congenital disorders. However, the mechanical stress and strain experienced by the developing human skeleton in utero have never before been characterized. Here, we quantify the biomechanics of fetal movements during the second half of gestation by modelling fetal movements captured using novel cine-magnetic resonance imaging technology. By tracking these movements, quantifying fetal kick and muscle forces, and applying them to three-dimensional geometries of the fetal skeleton, we test the hypothesis that stress and strain change over ontogeny. We find that fetal kick force increases significantly from 20 to 30 weeks' gestation, before decreasing towards term. However, stress and strain in the fetal skeleton rises significantly over the latter half of gestation. This increasing trend with gestational age is important because changes in fetal movement patterns in late pregnancy have been linked to poor fetal outcomes and musculoskeletal malformations. This research represents the first quantification of kick force and mechanical stress and strain due to fetal movements in the human skeleton in utero, thus advancing our understanding of the biomechanical environment of the uterus. Further, by revealing a potential link between fetal biomechanics and skeletal malformations, our work will stimulate future research in tissue engineering and mechanobiology