Prem Bhattarai

Background: Idiopathic pulmonary fibrosis (IPF) is an irreversible lung fibrotic disorder of unknown cause. It has been reported that bacterial and viral co-infections exacerbate disease pathogenesis. These pathogens use adhesion molecules such as platelet activating factor receptor (PAFR) and intercellular adhesion molecule-1 (ICAM–1) to gain cellular entry, causing infections. Methods: Immunohistochemical staining was carried out for lung resections from IPF patients (n = 11) and normal controls (n = 12). The quantification of PAFR and ICAM–1 expression is presented as a percentage in the small airway epithelium. Also, type 2 pneumocytes and alveolar macrophages were counted as cells per mm² of the parenchymal area and presented as a percentage. All image analysis was done using Image Pro Plus 7.0 software. Results: PAFR expression significantly increased in the small airway epithelium (p < 0.0001), type 2 pneumocytes (p < 0.0001) and alveolar macrophages (p < 0.0001) compared to normal controls. Similar trend was observed for ICAM–1 expression in the small airway epithelium (p < 0.0001), type 2 pneumocytes (p < 0.0001) and alveolar macrophages (p < 0.0001) compared to normal controls. Furthermore, the proportion of positively expressed type 2 pneumocytes and alveolar macrophages was higher in IPF than in normal control. Conclusions: This is the first study to show PAFR and ICAM–1 expression in small airway epithelium, type 2 pneumocytes and alveolar macrophages in IPF. These findings could help intervene microbial impact and facilitate management of disease pathogenesis.

Background: We have previously reported that endothelial-to-mesenchymal transition (EndMT) is an active process in patients with idiopathic pulmonary fibrosis (IPF) contributing to arterial remodelling. Here, we aim to quantify drivers of EndMT in IPF patients compared to normal controls (NCs). Methods: Lung resections from thirteen IPF patients and eleven NCs were immunohistochemically stained for EndMT drivers, including TGF-β1, pSmad-2/3, Smad-7, and β-catenin. Intima, media, and adventitia were analysed for expression of each EndMT driver in pulmonary arteries. Computer- and microscope-assisted Image ProPlus7.0 image analysis software was used for quantifications. Results: Significant TGF-β1, pSmad-2/3, Smad-7, and β-catenin expression was apparent across all arterial sizes in IPF (p < 0.05). Intimal TGF-β1, pSmad-2/3, Smad-7, and β-catenin were augmented in the arterial range of 100–1000 μm (p < 0.001) compared to NC. Intimal TGF-β1 and β-catenin percentage expression showed a strong correlation with the percentage expression of intimal vimentin (r′ = 0.54, p = 0.05 and r′ = 0.61, p = 0.02, respectively) and intimal N-cadherin (r′ = 0.62, p = 0.03 and r′ = 0.70, p = 0.001, respectively). Intimal TGF-β1 and β-catenin expression were significantly correlated with increased intimal thickness as well (r′ = 0.52, p = 0.04; r′ = 0.052, p = 0.04, respectively). Moreover, intimal TGF-β1 expression was also significantly associated with increased intimal elastin deposition (r′ = 0.79, p = 0.002). Furthermore, total TGF-β1 expression significantly impacted the percentage of DLCO (r′ = −0.61, p = 0.03). Conclusions: This is the first study to illustrate the involvement of active TGF-β/Smad-2/3-dependent and β-catenin-dependent Wnt signalling pathways in driving EndMT and resultant pulmonary arterial remodelling in patients with IPF. EndMT is a potential therapeutic target for vascular remodelling and fibrosis in general in patients with IPF.

Rationale: Pulmonary hypertension (PH) is usually diagnosed quite late, but vascular modifications have early onset in smokers and COPD patients. Here we aim to provide size-based morphometric quantification of pulmonary arterial changes in smokers, mild-moderate COPD compared to healthy non-smokers. Methods: Movat’s Pentachrome staining was carried out for lung resections from normal lung function smokers (NLFS, n=6), small airway disease, (SAD, n=9), COPD current (COPD-CS, n=9), and ex-smokers (COPD-ES, n=10) and healthy non-smoker control (NC, n=12). Arteries measuring 100-1000 micron were blindly analyzed for total number of arteries per parenchymal tissue density and arterial wall thickness using advanced imaging software Image ProPlus V7.0. Results: We found a significant increment in total parenchymal tissue density (p value<0.01) and decline in total arterial numbers across all arterial size ranges in pathological groups compared to NC (p<0.001). In small to medium arteries (100-400microns) the wall thickness in pathological groups was significantly thicker than NC(p<0.01). This increase in arterial thickness across (100-400microns) in COPD-CS group specifically affected FEV1/FVC (%), (Spearman r’= -0.87, -0.74, -0.77, & p=0.004,0.028,0.030 respectively). Interestingly, a reversible trend was noticed in arterial thickness in COPD-ES, significantly lesser to COPD-CS in ranges between100-300microns (p<0.05). Conclusion: Smoking contributed to both reduced numbers and increased thickness across all arterial sizes most evidently in COPD-CS, that reversed with smoking cessation.

The forced oscillation technique (FOT) is a non-invasive method to assess airway function by emitting oscillatory signals into the respiratory tract during tidal ventilation. This opinion piece discusses the current use, trialled modification and future directions in utilizing FOT as a novel diagnostic tool for early detection of small airway changes in smokers. The published evidence to date has shown that FOT parameters could be a sensitive diagnostic tool to detect early respiratory changes in smokers. Multiple frequencies and the frequency dependence of resistance and reactance can provide the most valuable and early information regarding smoking induced changes in airways. Considering its non-invasiveness, lower level of discomfort to patients than spirometry, feasibility, and cost effectiveness, it could be the first-choice diagnostic technique for detection of early respiratory changes in smokers. The finding of FOT could further be supported and correlated with inflammatory markers.

Background: Self-medication is the use of drugs to treat self-diagnosed disorders/symptoms, or the intermittent/continued use of a prescribed drug for chronic/recurrent disease/symptoms (WHO). It is the cause for antibiotic resistance, inappropriate treatment, financial burden and many deaths. WHO listed self-medication as one of the priority research area at the local context. The objective of the study was to find the prevalence and pattern of self-medication in surrounding communities of Birat Medical College and Teaching Hospital. Methods: A community-based cross-sectional study was conducted at the surrounding communities of Birat Medical College from 1st August 2018 to 15th December 2018. Multistage sampling was used to collect information from 348 household having family members aged 16 years and above. Ethical approval was taken from Institutional Review Committee of Birat Medical College. Pre-tested semi-structured questionnaire was used. Results: The mean age of the participants was 40.5±15.9 years. Prevalence of self-medication was 44.04%. Majority took self-medication for headache 43.6% followed by common cold 39.1% etc. Majority used allopathic drugs 82.7% followed by traditional healers 9.8%. Common medication were antipyretics 18.8%, antibiotics 16.5%, proton pump inhibitor 7.5%, antihistamines 6.8% etc. The reason behind self-medication were low cost 30.1%, time saving 24.1%, illness too trivial/mild for consultation 18.8%, quick relief 18.1%, high doctor fee 15 %, lack of awareness 13.5 %, familiar with treatment options 12.8%, long waiting line in hospital 12% etc. Out of them 8.3% noticed side effects of self-medication. Out of all 59.5% felt the need of awareness program on rational use of medicines. Age, sex, marital status, ethnicity, religion, education and occupation of participants, education and occupation of head of household, poverty status, family type, house residence type, type of house has no significant association with self-medication. Participants residing in alani/rent households were 1.93 times more likely to self-medicate than those residing in their own and participants having negative attitude were 1.90 times more likely to self-medicate than those who had positive attitude and both were statistically significant. Conclusions: The burden of self-medication was present and allopathic drugs including antibiotics were common. Adverse drug reactions were reported but participants were unaware about the place to report. Participants had negative attitude towards self-medication which is harmful for their health. As pharmacy was the common source of self-medication, the prescription based medicine dispensary should be advocated.

Introduction: The different mood states in our daily life can affect our mental and emotional health. The aim of our study was to explore photoplethysmography to record heart rate variability as a marker of changes in mood states in our daily life.Materials and Methods: Two groups of affective pictures categorized into positive and negative sets were shown to thirty subjects on two different consecutive days with simultaneously recording of heart rate variability for 5 minutes by photoplethysmography technique. Immediately after recording on each day, 0-9 self-assessment scale was used to assess the mood state of the subject after viewing the set of pictures.Results: Sympathetic domains of heart rate variability like low frequency (200.3 ±4.1 vs. 166.7 ±2.8, p<0.05), low- and high frequency ratio (1.45 ± 0.21 vs. 0.55 ± 0.07, p<0.05) and low frequency (55.8 ± 2.9 vs. 38.6 ± 2.8, p<0.05) significantly increased in negative mood state condition as compared to positive mood state condition. High frequency (157.9 ± 3.9 vs. 264.3 ± 5.3, p<0.05) and high frequency (44 ± 2.9 vs. 61.2 ±4.2, p< 0.05) significantly increased in positive mood state condition as compared to negative mood state condition. There was significant increase in heart rate (78 ± 2.99 vs. 73 ± 3.11, p<0.05) in negative mood state as compared to positive mood state.Conclusions: Increase in sympathetic activity during negative mood state and increase in parasympathetic activity during positive mood state measured by photoplethysmography technique validates this easy and noninvasive mental assessment tool to determine different mood states.

Introduction: Nepal like many other developing countries in the world is witnessing the rapid ageing of population. Quality of life (QOL) of elderly people is becoming even more relevant towards an ageing society. In Nepal, less is known regarding special needs and quality of life of elderly people either in familial situations or in old age residences. Objectives: The present study was undertaken to assess and compare the quality of life of elderly living with the family and in old age home. Methodology: A Cross sectional descriptive study was conducted from October 2016 to April 2017 among elderly population aged 60 years and above. A total of 50 elderly people were enrolled from old age home (OAH) using total enumeration sampling technique and equal number of sample was selected from the family setting. QOL of elderly was assessed using WHOQOL-BRIEF questionnaire after taking informed consent from the participants. Data was analyzed using SPSS. Results: The mean scores of QOL domains were better among the age group 60-70 years, males, married, literates and who had children. The mean scores of QOL in physical, psychological and environmental domains were better in elderly living with the family than living in OAH. Low scores were found on social domain among elderly compared to other domain irrespective of their residence. Conclusion: QOL score among elderly is average, while social relationship domain of QOL scores was found to be low. Social activities should be expanded for these residents in order to promote social health. The QOL which each individual possesses is very important in all aspects be it physical, psychological, social & environmental. Furthermore, programs that help elderly people live in their own homes and social environments should be promoted.BIBECHANA 16 (2019) 221-227

Despite the successful adaptation to high altitude, some differences do occur due to long term exposure to the hypoxic environment. The effect of long term high altitude exposure on cardiac autonomic adjustment during basal and post-exercise recovery is less known. Thus we aimed to study the differences in basal cardiac autonomic adjustment and its response to exercise in highlanders and to compare it with lowlanders. The study was conducted on 29 healthy highlander males who were born and brought up at altitude of 3000 m and above from the sea level, their cardiac autonomic adjustment was compared with age, sex, physical activity and ethnicity-matched 29 healthy lowlanders using Heart Rate Variability (HRV) during rest and recovery from sub-maximal exercise (3 m step test). Intergroup comparison between the highlanders and lowlanders and intragroup comparison between the rest and the postexercise recovery conditions were done. Resting heart rate and HRV during rest was comparable between the groups. However, heart rate recovery after 3 min step test was faster in highlanders (p < 0.05) along with significantly higher LF power and total power during the recovery phase. Intragroup comparison of highlanders showed higher SDNN (p < 0.05) and lower LF/HF ratio (p < 0.05) during recovery phase compared to rest which was not significantly different in two phases in lowlanders. Further highlander showed complete recovery of RMSSD, NN50, pNN50 and HF power back to resting level within five minutes, whereas, these parameters failed to return back to resting level in lowlanders within the same time frame. Highlanders completely recovered back to their resting state within five minutes from cessation of step test with parasympathetic reactivation; however, recovery in lowlanders was delayed.

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