Correlation between impulse oscillometry with bronchodilator reversibility in asthmatic population in a tertiary referral centre.

INTRODUCTION: Spirometry is considered as a 'gold standard' for diagnosis of asthma. Impulse oscillometry (IOS) is an alternative diagnostic tool which requires less cooperation by the participants. We performed a study to determine the correlation of IOS with bronchodilator reversibility from spirometry in asthmatic participants. We studied the correlation between forced expiratory flow (FEF25%-75%) and differences between the resistance at 5Hz and 20Hz (R5-R20) in small airway disease (SAD) and the proportion of SAD diagnosed using IOS. MATERIALS AND METHODS: This was a cross-sectional study involving 82 asthmatic participants in Hospital Canselor Tuanku Muhriz (HCTM), Universiti Kebangsaan Malaysia (UKM) conducted between December 2020 till January 2022. Participants performed pre- and post-bronchodilator IOS and spirometry within the same day. Correlation between spirometry and IOS parameters and FEF25%-75% with IOS were determined and analysed. RESULTS: The change of forced expiratory volume in 1 second (FEV1) was statistically correlated with a change of R5 in IOS. A decrement of 14.5% in R5 can be correlated with positive bronchodilator response (BDR) with a sensitivity of 63.9% and specificity of 60.9%, p=0.007. Pre-bronchodilator FEF25%-75% correlated with all parameters of SAD in IOS, e.g., R5-R20, reactance at 5Hz (X5) and area of reactance (AX), p < 0.05. IOS detection for SAD is higher compared to FEF25%-75% in the BDR negative group (91.3% vs 58.7%). CONCLUSION: IOS detected both bronchodilator reversibility and SAD hence can be considered as an alternative tool to spirometry for diagnosis of asthma in adults. IOS detected SAD more than FEF25%-75%, especially in BDR-negative group.

Comparison of clinical efficacy and satisfaction of Tiotropium via Respimat® administration with and without a spacer in patient with Chronic Obstructive Pulmonary Disease: A single centre experience.

OBJECTIVE: This study assessed the delivery of tiotropium via Respimat® in addition to standard care of treatment among chronic obstructive pulmonary disease (COPD) patients. We study the efficacy, clinical outcome of handling inhaler device, rate of exacerbation and frequency of hospital admission of tiotropium via Respimat® with and without the use of a spacer (AeroChamber®). METHODS: Randomised, open-label study of COPD patients which was randomised into two groups: spacer or nonspacer groups using tiotropium via Respimat®. Treatment with their pre-existing inhalers continued. Subjects were assessed at weeks 0, and 8 for forced expiratory volume in 1 second (FEV1), COPD assessment tool (CAT), St. George's Respiratory Questionnaire (SGRQ), and satisfaction questionnaire. RESULTS: We enrolled 96 subjects: 49 in the spacer group and 47 in the non-spacer group. The mean predicted FEV1 in spacer group was 54.48% at baseline and 57.5l% at week 8: p=0.011. In the non-spacer groups, FEV1 was 54.48% at baseline and 59.20% with a mean increment of 4.72 in both groups: p=0.002. There were no difference of exacerbation rates and hospital admission between both groups. At baseline, mean CAT score in the spacer group was 14.01 which improved to 9.80 (p<0.001) and 14.01 to 8.80 (p<0.001) in the non-spacer group. SGRQ total score reduced in both groups with mean difference of 3.1 (p<0.001) and 3.7: (p<0.001) at weeks 0 to 8. CONCLUSION: There was no difference between exacerbation and hospital admissions between both groups. There was no difference in FEV1, CAT and SQRQ score using Tiotropium via Respimat® with or without a spacer.

Correlation between blood pressure and lung function in Malaysian adult population.

INTRODUCTION: The correlation between pulmonary function and hypertension remains ambiguous. This study therefore determined the relationship between pulmonary function and hypertension among adult subgroup in Malaysia. MATERIALS AND METHODS: Data for this study were obtained from an ongoing Prospective Urban Rural Epidemiology- Rural Urban Study (PURE RUS) , which is a prospective cohort study done by MARA University of Technology (UiTM) Medical Faculty research team to track risk factors, changing lifestyles, and chronic diseases in rural and urban population. The inclusion criteria included: Malaysian citizen, age 18-80 years, not on any anti-hypertensive agents, and able to perform lung function test. 1640 participants satisfied the criteria and were recruited in this study. RESULTS: From the studied population, males comprised 43.5% of them and female comprised 56.5%. A significant inverse relationship was found between pulmonary function and systolic blood pressure in both sexes measured by forced vital capacity (FVC) and Forced Expiratory Volume in 1 second (FEV1). A substantial inverse relationship was also found between pulmonary function and age, and there was a profound positive association between blood pressure and age. No major disparities were significant in pulmonary function between hypertensive and age-matched normotensive participants. CONCLUSION: Even though a substantial inverse relationship was evident between systolic blood pressure and pulmonary function, its precise clinical importance needs to be further explored particularly when age can influence both pulmonary function and blood pressure. Clearly, the impact of age has to be removed before FVC can be used as a prognosticator of hypertension.

SKA-31, an activator of Ca2+-activated K+ channels, improves cardiovascular function in aging.

Aging represents an independent risk factor for the development of cardiovascular disease, and is associated with complex structural and functional alterations in the vasculature, such as endothelial dysfunction. Small- and intermediate-conductance, Ca2+-activated K+ channels (KCa2.3 and KCa3.1, respectively) are prominently expressed in the vascular endothelium, and pharmacological activators of these channels induce robust vasodilation upon acute exposure in isolated arteries and intact animals. However, the effects of prolonged in vivo administration of such compounds are unknown. In our study, we hypothesized that such treatment would ameliorate aging-related cardiovascular deficits. Aged (∼18 months) male Sprague Dawley rats were treated daily with either vehicle or the KCa channel activator SKA-31 (10 mg/kg, intraperitoneal injection; n = 6/group) for 8 weeks, followed by echocardiography, arterial pressure myography, immune cell and plasma cytokine characterization, and tissue histology. Our results show that SKA-31 administration improved endothelium-dependent vasodilation, reduced agonist-induced vascular contractility, and prevented the aging-associated declines in cardiac ejection fraction, stroke volume and fractional shortening, and further improved the expression of endothelial KCa channels and associated cell signalling components to levels similar to those observed in young male rats (∼5 months at end of study). SKA-31 administration did not promote pro-inflammatory changes in either T cell populations or plasma cytokines/chemokines, and we observed no overt tissue histopathology in heart, kidney, aorta, brain, liver and spleen. SKA-31 treatment in young rats had little to no effect on vascular reactivity, select protein expression, tissue histology, plasma cytokines/chemokines or immune cell properties. Collectively, these data demonstrate that administration of the KCa channel activator SKA-31 improved aging-related cardiovascular function, without adversely affecting the immune system or promoting tissue toxicity.

Uncovering anti-inflammatory potential of Lantana camara Linn: Network pharmacology and in vitro studies.

Lantana camara Linn contains a diverse array of metabolites that exhibit therapeutic potential. The aim of this study was to evaluate the potential of L. camara leaves, which were collected at the Ie-Seu'um geothermal area in Aceh, Indonesia, as an anti-inflammatory through network pharmacology and in vitro analysis. The ethanolic extract derived from L. camara underwent identification utilizing gas chromatography-mass spectrometry (GC-MS) to verify chemical constituents for drug-likeness properties. The evaluation of anti-inflammatory activity included network pharmacology and a series of in vitro investigations using two methods: protein inhibition and albumin denaturation assays. The findings revealed that the extract contained a domination of terpenoids and fatty acids class, which met the evaluation criteria of drug-likeness. Network pharmacology analysis identified the top five key proteins (peroxisome proliferator-activated receptor gamma, prostaglandin G/H synthase 2, epidermal growth factor receptor, hypoxia-inducible factor 1-alpha, and tyrosine protein kinase-Janus kinase 2) involved in inflammation-related protein-protein interactions. Gene ontology enrichment highlighted the predominance of inflammatory responses in biological processes (BP), cytoplasm in cellular components (CC), and oxidoreductase activity in molecular functions (MF). In vitro analysis showed that the extract inhibited protein activity and protein denaturation with inhibitory concentration (IC50) values of 202.27 and 223.85 ppm, respectively. Additionally, the extract had antioxidant activity with DPPH- and ABTS-scavenging IC50 values of 140 ppm and 163 ppm, respectively. Toxicological assessment by brine shrimp lethality assay (BSLA), yielding a lethal concentration (LC50) value of 574 ppm (essentially non-toxic) and its prediction via ProTox 3.0 that indicated non-active in hepatotoxicity, carcinogenicity, immunotoxicity, mutagenicity, and cytotoxicity. These results suggested that L. camara holds noteworthy effectiveness as a potential candidate for complementary medicine in the realm of inflammatory agents, warranting further investigation in clinical settings.

Low dose intrapleural alteplase and pulmozyme (DNase) in two post-surgical patients with pleural sepsis.

Alteplase and pulmozyme (DNase) administered intrapleurally have revolutionised the management of pleural infection in the last decade. However, the use of intrapleural fibrinolytic has not been well established in high risks patients. Here, we describe 2 patients with high risk of bleeding due to recent surgery who developed empyema; successfully treated with these medications. The first patient was a 36-year-old female post oesophagectomy for oesophageal carcinoma, complicated with anastomotic leak and empyema; and the second patient was a 56-year-old female post percutaneous nephrolithotomy for right obstructive uropathy who developed right-sided empyema. Both patients were treated successfully with 3 doses of intrapleural alteplase 2.5 mg and DNase 5 mg without any major adverse effects. This case report adds to the current literature on the safety of intrapleural fibrinolytics and highlights that lower doses of alteplase in combination with pulmozyme is efficacious and may be considered in high-risk patients.