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Introduction We investigated the prevalence of children’s exposure to secondhand smoke (SHS) in the car of their parents/guardians and the associated factors. Methods A self-administered validated questionnaire was used to obtain data from the nationally representative samples of school-going adolescents aged 11–19 years in Malaysia. Prevalence rates were computed and chi-squared tests and multiple logistic regression were conducted. Results Of the participants, 23.3% reported exposure to SHS at least once in the car of their parents/guardians during the last 7 days before the survey. The prevalence and likelihood of SHS exposure were significantly higher in Malays, descendants of natives of Sabah and Sarawak, schools in rural areas, females, and current smokers. However, age group and knowledge on the harmful effects of SHS were not significant after adjusting for confounding effects. Conclusions A substantial proportion of school-going adolescents were exposed to secondhand smoke in the car of their parents/guardians. This highlights the need for effective tobacco control measures to include health promotion and smoke-free car regulations to be introduced to prevent severe health hazards and to reduce smoking initiation among non-smoking adolescents.

Objectives: The study aims to study 1) how to use traditional medicine in the health of women and children of the Togutil tribe, and describes 2) the local wisdom of forest conservation by the Toguti tribe., Methods: The research used ethnography study with the design of multiple sites and a tick description approach (thick description and depth)., Results: Togutil women and children always rely on traditional medicine and they do this treatment since ancient times and have always been done from generation to generation. Traditional medicinal ingredients come from the leaves, stems, roots of trees, and fruit of the trees. If the medicine has been given and there is no change, the person who is sick will be taken to a doctor for consultation and recommend other traditional medicine to drink. The role of women and children of the Togutil tribe is more dominant in the home to maintaining the food security and the role of men of the Togutil tribe is outside the home to hunting and farming., Conclusion: The health of Togutil women and children is very important to maintain their survival. The pattern of maintaining their health by consuming traditional medicines., (Copyright © 2021 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: p38 mitogen-activated protein kinase (MAPK) plays a central role in the regulation and activation of pro-inflammatory mediators. COPD patients have increased levels of activated p38 MAPK, which correlate with increased lung function impairment, alveolar wall inflammation, and COPD exacerbations., Objectives: These studies aimed to assess the effect of p38 inhibition with AZD7624 in healthy volunteers and patients with COPD. The principal hypothesis was that decreasing lung inflammation via inhibition of p38α would reduce exacerbations and improve quality of life for COPD patients at high risk for acute exacerbations., Methods: The p38 isoform most relevant to lung inflammation was assessed using an in situ proximity ligation assay in severe COPD patients and donor controls. Volunteers aged 18-55 years were randomized into the lipopolysaccharide (LPS) challenge study, which investigated the effect of a single dose of AZD7624 vs placebo on inflammatory biomarkers. The Proof of Principle study randomized patients aged 40-85 years with a diagnosis of COPD for >1 year to AZD7624 or placebo to assess the effect of p38 inhibition in decreasing the rate of exacerbations., Results: The p38 isoform most relevant to lung inflammation was p38α, and AZD7624 specifically inhibited p38α and p38β isoforms in human alveolar macrophages. Thirty volunteers were randomized in the LPS challenge study. AZD7624 reduced the increase from baseline in sputum neutrophils and TNF-α by 56.6% and 85.4%, respectively ( p <0.001). In the 213 patients randomized into the Proof of Principle study, there was no statistically significant difference between AZD7624 and placebo when comparing the number of days to the first moderate or severe exacerbation or early dropout., Conclusion: Although p38α is upregulated in the lungs of COPD patients, AZD7624, an isoform-specific inhaled p38 MAPK inhibitor, failed to show any benefit in patients with COPD., Competing Interests: Disclosure NRP, DMC, MF, ZT, SA, THM, SL, KP, NK, EE, CK, KK, RP, MNB, SIR, and PJ are AstraZeneca employees and hold stocks or shares in AstraZeneca. SL, SG, LS, and GWC no longer work for AstraZeneca or Quintiles Drug Research Unit at Guy’s Hospital, but were employees of the companies at the time of this work. BJM is an advisory board member for AstraZeneca. No author received reimbursement for the preparation of this report. The authors report no other conflicts of interest in this work.

In this perspective article, we discuss, from a statistician's perspective, how biomarkers can be useful in decision making in drug development with emphasis on early clinical development (Phase I and II) in chronic obstructive pulmonary disease. We illustrate with examples of how biomarkers can affect the very choice of treatment strategy: for example, targeting patients in early versus late phases of the disease or patients with particular extrapulmonary manifestations of chronic obstructive pulmonary disease. We also illustrate the use of biomarkers for establishing proof of mechanism in Phase I trials and how surrogate biomarkers can be used as end points in Phase II leading to shorter and more efficient proof-of-principle and dose-finding trials.

Background: To describe a study design that focuses on risk factors and patterns of chronic obstructive pulmonary disease (COPD) exacerbations., Methods: A 2-year, single centre, observational study was conducted in Guangzhou in China. The study enrolled 318 subjects with COPD aged 40-79 years, stratified into different but equally sized groups according to global initiative for chronic obstructive lung disease (GOLD) stage (including Stage 0) and 86 lung healthy controls. An assessment each year was scheduled including questionnaires, lung function testing, Chest X-ray and blood collection. A sub-group, called sub-group X, consisting of 203 subjects with COPD and 51 lung healthy controls, was selected to answer a symptom questionnaire daily (EXACT-PRO) via a BlackBerry Personal Digital Assistant (PDA) device. Upon an alert that indicated a change in daily symptom pattern, the patients were contacted by the clinic to decide whether they had experienced an exacerbation and should have an extra visit within 24-48 hours. At an extra visit, nasal and throat swabs, induced sputum and blood were collected. Air pollution, temperature and humidity were also monitored daily. A subset of sub-group X, called sub-group M that consisted of 52 COPD patients and 15 healthy controls was dedicated to measure muscle strength and a dexa scan., Results: More than 78% of the enrolled patients completed the study successfully. There appeared a difference between the patient groups and the controls in gender, age, body mass index (BMI), forced expiratory volume in 1 second (FEV1), FEV1/FVC and smoking at baseline. In sub-group X 90 out of 203 (44.4%) selected COPD patients developed one or more exacerbations in the 2-year observation period. They were more severe COPD patients according to GOLD stage at study start. On average most exacerbations occurred in the month March and the least number of exacerbations occurred in October., Conclusions: This study with the obtained patient dataset will allow a better insight in many aspects of exacerbations in COPD (e.g., the identification, the risk factors, phenotypes and the biomarkers).

Clear evidence for an association between systemic inflammation and increased arterial stiffness in patients with chronic obstructive pulmonary disease (COPD) is lacking. Moreover, the effects of pulmonary rehabilitation on arterial stiffness are not well studied. We aimed to 1) confirm increased arterial stiffness in COPD; 2) evaluate its correlates including systemic inflammation; and 3) study whether or not it is influenced by pulmonary rehabilitation. Aortic pulse-wave velocity (APWV) was determined in 168 healthy volunteers, and APWV and inflammatory markers were determined in 162 COPD patients during baseline evaluation of a pulmonary rehabilitation programme. A complete post-pulmonary rehabilitation dataset was collected in 129 patients. It was found that APWV was increased in COPD patients when compared with controls, blood pressure and age predicted baseline APWV, and systemic inflammatory markers were not independently related to APWV. Although baseline APWV was predictive for the change in APWV after pulmonary rehabilitation (r= -0.77), on average APWV did not change (10.7 ± 2.7 versus 10.9 ± 2.5 m·s(-1); p=0.339). Arterial stiffness in COPD is not related to systemic inflammation and does not respond to state-of-the-art pulmonary rehabilitation. These results emphasise the complexity of cardiovascular risk and its management in COPD.

Microchip arrays have become one of the most rapidly growing techniques for monitoring gene expression at the genomic level and thereby gaining valuable insight about various important biological mechanisms. Examples of such mechanisms are: identifying disease-causing genes, genes involved in the regulation of some aspect of the cell cycle, etc. In this article, we discuss the problem of estimating gene expression based on a proper statistical model. More precisely, we show how the model introduced by Li and Wong can be used in its full bivariate generality to provide a new measure of gene expression from high-density oligonucleotide arrays. We also present a second gene expression index based on a new way of reducing the model into a simpler univariate model. In both cases, the gene expression indices are shown to be unbiased and to have lower variance than the established ones. Moreover, we present a bootstrap method aiming at providing non-parametric confidence intervals for the expression index.

The most recurrent BRCA1/BRCA2 mutation in Sweden is the BRCA1 mutation 3171ins5. In the western part of Sweden this mutation accounts for as much as 77% of identified mutations in these two genes. Our aim was to analyse in detail the haplotype and founder effects of the 3171ins5 and furthermore attempt to estimate the time of origin of the mutation. In the study we included eighteen apparently unrelated families with hereditary breast and/or ovarian cancer. At least one individual in each family had previously tested positive for the 3171ins5 mutation. Polymorphic microsatellite markers were used for the haplotype analyses. The markers were located within or flanking the BRCA1 gene spanning a region of 17.3 cM. We found several different haplotypes both for disease alleles and for the normal alleles. However, a conserved haplotype of 3.7 cM was observed in the 3171ins5 carriers spanning over four markers located within or very close to the BRCA1 gene. As this haplotype was not present in any of the normal controls it is highly likely that this is a mutation identical by descent, i.e. a true founder. The results from the haplotype analyses were used to estimate the age of the mutation. Estimations based on the P(excess) and linkage disequilibrium gives a first appearance of the mutation sometime around the 6th century, approximately 50 generations ago.