Essential oil composition of passiflora foetida L. (passifloraceae) flowers and chemical-biology study of the leaves extracts and isolated compound.

Passiflora foetida is a climbing herb employed in ethno-medicine for the treatment of various ailments. The essential oil from flowers of P. foetida was obtained by hydrodistillation. The ethanol extract of the leaves was dissolved in water, then partitioned with n-hexane and n-butanol to obtain the various fractions; the fractions and isolated compound were subjected to in vitro antioxidant activity. Gas chromatography-mass spectrometry afforded the identification of forty-two constituents in the floral oil, dominated by ß-caryophyllene (17.2%), cedrol (11.5%), and α-humulene (11.5%). The n-butanol fraction was the most active (70% inhibition and absorbance 0.401; 100 µg/mL) in the 2,2-diphenyl-1-picrylhydrazyl radicals and ferric reducing power assays, respectively. Chromatographic analysis facilitated the isolation of 8-C-ß-d-glucosylapigenin (vitexin) from the butanol fraction of P. foetida. Vitexin demonstrated good antioxidant activities (75% inhibition and absorbance 0.424; 100 µg/mL) compared with ascorbic acid. The volatile metabolites of P. foetida flowers are reported for the first time.

Can We Use Lung Function Thresholds and Respiratory Symptoms to Identify Pre-COPD? A Prospective, Population-based Cohort Study.

RATIONALE: The term 'pre-COPD' refers to individuals at high-risk of developing Chronic Obstructive Pulmonary Disease (COPD) who do not meet conventional spirometric criteria for airflow obstruction. New approaches to identifying these individuals are needed, particularly in younger populations. OBJECTIVE: To determine whether lung function thresholds and respiratory symptoms can be used to identify individuals at-risk of developing COPD. METHODS: The Tasmanian Longitudinal Health Study is a population-based cohort first studied in 1968 (age 7). Respiratory symptoms, pre- and post-bronchodilator (BD) spirometry, diffusing capacity and static lung volumes were measured on a subgroup at age 45, and incidence of COPD was assessed at age 53. For each lung function measure, z-scores were calculated using Global Lung Initiative references. The optimal threshold for best discrimination of COPD incidence was determined by the unweighted Youden Index. MEASUREMENTS AND MAIN RESULTS: Among 801 participants who did not have COPD at age 45, the optimal threshold for COPD incidence by age 53 was pre-BD FEV1/FVC z-score < -1.264, corresponding to the lowest 10th percentile. Those below this threshold had 36-fold increased risk of developing COPD over an eight-year follow-up period (RR 35.8, 95%CI 8.88 to 144), corresponding to a risk difference of +16.4% (95%CI 3.7-67.4). The sensitivity was 88% and specificity 87%. Positive and negative likelihood ratios were 6.79 and 0.14, respectively. Respiratory symptoms, post-BD spirometry, diffusing capacity and static lung volumes did not improve on the classification achieved by pre-BD FEV1/FVC alone. CONCLUSION: Our findings support the inclusion of pre-BD spirometry in the physiological definition of pre-COPD and indicate that pre-BD FEV1/FVC at the 10th percentile accurately identifies individuals at high-risk of developing COPD in community-based settings.

Association of novel adult cough subclasses with clinical characteristics and lung function across six decades of life in a prospective, community-based cohort in Australia: an analysis of the Tasmanian Longitudinal Health Study (TAHS).

BACKGROUND: Cough is a common yet heterogeneous condition. Little is known about the characteristics and course of cough in general populations. We aimed to investigate cough subclasses, their characteristics from childhood across six decades of life, and potential treatable traits in a community-based cohort. METHODS: For our analysis of the Tasmanian Longitudinal Health Study (TAHS), a prospective, community-based cohort study that began on Feb 23, 1968, and has so far followed up participants in Tasmania, Australia, at intervals of 10 years from a mean age of 7 years to a mean age of 53 years, we used data collected as part of the TAHS to distinguish cough subclasses among current coughers at age 53 years. For this analysis, participants who answered Yes to at least one cough-related question via self-report questionnaire were defined as current coughers and included in a latent class analysis of cough symptoms; participants who answered No to all nine cough-related questions were defined as non-coughers and excluded from this analysis. Two groups of longitudinal features were assessed from age 7 years to age 53 years: previously established longitudinal trajectories of FEV1, forced vital capacity [FVC], FEV1/FVC ratio, asthma, and allergies-identified via group-based trajectory analysis or latent class analysis-and symptoms at different timepoints, including asthma, current productive cough, ever chronic productive cough, current smoking, and second-hand smoking. FINDINGS: Of 8583 participants included at baseline in the TAHS, 6128 (71·4%) were traced and invited to participate in a follow-up between Sept 3, 2012, and Nov 8, 2016; 3609 (58·9%) of these 6128 returned the cough questionnaire. The mean age of participants in this analysis was 53 years (SD 1·0). 2213 (61·3%) of 3609 participants were defined as current coughers and 1396 (38·7%) were categorised as non-coughers and excluded from the latent class analysis. 1148 (51·9%) of 2213 participants in this analysis were female and 1065 (48·1%) were male. Six distinct cough subclasses were identified: 206 (9·3%) of 2213 participants had minimal cough, 1189 (53·7%) had cough with colds only, 305 (13·8%) had cough with allergies, 213 (9·6%) had intermittent productive cough, 147 (6·6%) had chronic dry cough, and 153 (6·9%) had chronic productive cough. Compared with people with minimal cough, and in contrast to other cough subclasses, people in the chronic productive cough and intermittent productive cough subclasses had worse lung function trajectories (FEV1 persistent low trajectory 2·9%, 6·4%, and 16·1%; p=0·0011, p<0·0001; FEV1/FVC early low-rapid decline trajectory 2·9%, 12·1%, and 13·0%; p=0·012, p=0·0007) and a higher prevalence of cough (age 53 years 0·0%, 32·4% [26·1-38·7], and 50·3% [42·5-58·2]) and asthma (age 53 years 6·3% [3·7-10·6], 26·9% [21·3-33·3], and 41·7% [24·1-49·7]) from age 7 years to age 53 years. INTERPRETATION: We identified potential treatable traits for six cough subclasses (eg, asthma, allergies, and active and passive smoking for productive cough). The required management of productive cough in primary care (eg, routine spirometry) might differ from that of dry cough if our findings are supported by other studies. Future population-based studies could apply our framework to address the heterogeneity and complexity of cough in the community. FUNDING: The National Health and Medical Research Council of Australia, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, Victorian Asthma Foundation, Queensland Asthma Foundation, Tasmanian Asthma Foundation, The Royal Hobart Hospital Research Foundation, the Helen MacPherson Smith Trust, GlaxoSmithKline, and the China Scholarship Council.

Longitudinal Asthma Phenotypes from Childhood to Middle-Age: A Population-based Cohort Study.

Rationale: Asthma is a heterogeneous condition, and longitudinal phenotyping may provide new insights into the origins and outcomes of the disease. Objectives: We aimed to characterize the longitudinal phenotypes of asthma between the first and sixth decades of life in a population-based cohort study. Methods: Respiratory questionnaires were collected at seven time points in the TAHS (Tasmanian Longitudinal Health Study) when participants were aged 7, 13, 18, 32, 43, 50, and 53 years. Current-asthma and ever-asthma status was determined at each time point, and group-based trajectory modeling was used to characterize distinct longitudinal phenotypes. Linear and logistic regression models were fitted to investigate associations of the longitudinal phenotypes with childhood factors and adult outcomes. Measurements and Main Results: Of 8,583 original participants, 1,506 had reported ever asthma. Five longitudinal asthma phenotypes were identified: early-onset adolescent-remitting (40%), early-onset adult-remitting (11%), early-onset persistent (9%), late-onset remitting (13%), and late-onset persistent (27%). All phenotypes were associated with chronic obstructive pulmonary disease at age 53 years, except for late-onset remitting asthma (odds ratios: early-onset adolescent-remitting, 2.00 [95% confidence interval (CI), 1.13-3.56]; early-onset adult-remitting, 3.61 [95% CI, 1.30-10.02]; early-onset persistent, 8.73 [95% CI, 4.10-18.55]; and late-onset persistent, 6.69 [95% CI, 3.81-11.73]). Late-onset persistent asthma was associated with the greatest comorbidity at age 53 years, with increased risk of mental health disorders and cardiovascular risk factors. Conclusions: Five longitudinal asthma phenotypes were identified between the first and sixth decades of life, including two novel remitting phenotypes. We found differential effects of these phenotypes on risk of chronic obstructive pulmonary disease and nonrespiratory comorbidities in middle age.

Biomarkers of asthma relapse and lung function decline in adults with spontaneous asthma remission: A population-based cohort study.

BACKGROUND: The extent to which biomarkers of asthma activity persist in spontaneous asthma remission and whether such markers are associated with future respiratory outcomes remained unclear. We investigated the association between sub-clinical inflammation in adults with spontaneous asthma remission and future asthma relapse and lung function decline. METHODS: The Tasmanian Longitudinal Health Study is a population-based cohort (n = 8583). Biomarkers of systemic inflammation were measured on participants at age 45, and latent profile analysis was used to identify cytokine profiles. Bronchial hyperresponsiveness (BHR) and nitric oxide products in exhaled breath condensate (EBC NOx) were measured at age 50. Participants with spontaneous asthma remission at ages 45 (n = 466) and 50 (n = 318) were re-evaluated at age 53, and associations between baseline inflammatory biomarkers and subsequent asthma relapse and lung function decline were assessed. RESULTS: We identified three cytokine profiles in adults with spontaneous asthma remission: average (34%), Th2-high (42%) and Th2-low (24%). Compared to the average profile, a Th2-high profile was associated with accelerated decline in post-BD FEV1 /FVC (MD -0.18% predicted per-year; 95% CI -0.33, -0.02), while a Th2-low profile was associated with accelerated decline in both post-BD FEV1 (-0.41%; -0.75, -0.06) and post-BD FVC (-0.31%; -0.62, 0.01). BHR and high TNF-α during spontaneous remission were associated with an increased risk of asthma relapse. In contrast, we found no evidence of association between EBC NOx and either asthma relapse or lung function decline. CONCLUSION: BHR and serum inflammatory cytokines have prognostic value in adults with spontaneous asthma remission. At-risk individuals with BHR, Th2-high or Th2-low cytokine profiles may benefit from closer monitoring and on-going follow-up.

Small for gestational age is associated with reduced lung function in middle age: A prospective study from first to fifth decade of life.

BACKGROUND AND OBJECTIVE: The association between birth weight, particularly relative to gestational age, and adult lung function is uncertain. We investigated the associations between birth weight relative to gestational age and measures of lung function in middle age, and mediation of these associations by adult height. METHODS: Participants in the Tasmanian Longitudinal Health Study who had both known birth weight and lung function assessment at age 45 years were included (n = 849). Linear regression models were fitted to investigate the association between small for gestational age and birth weight with post-bronchodilator lung function measures (forced expiratory volume in 1 second [FEV1 ], forced vital capacity [FVC], FEV1 /FVC, diffusing capacity for carbon monoxide [DL co], residual volume [RV] and total lung capacity [TLC]), adjusting for potential confounders. The contribution of adult height as a mediator of these associations was investigated. RESULTS: Compared with infants born with normal weight for gestational age, those born small for gestational age had reduced FEV1 (coefficient: -191 ml [95%CI: -296, -87]), FVC (-205 ml [-330, -81]), TLC (-292 ml [-492, -92]), RV (-126 ml [-253, 0]) and DL co (-0.42 mmol/min/kPa [-0.79, -0.041]) at age 45 years. However, they had comparable FEV1 /FVC. For every 1 kg increase in birth weight, lung function indices increased by an average of 117 ml (95%CI: 40, 196) for FEV1 , 124 ml (30, 218) for FVC, 215 ml (66, 365) for TLC and 0.36 mmol/min/kPa (0.11, 0.62) for DL co, independent of gestational age, but again not for FEV1 /FVC. These associations were significantly mediated by adult height (56%-90%). CONCLUSION: Small for gestational age was associated with reduced lung function that is likely due to smaller lungs with little evidence of any specific parenchymal impairment.

Childhood 'bronchitis' and respiratory outcomes in middle-age: a prospective cohort study from age 7 to 53 years.

BACKGROUND: Chronic bronchitis in childhood is associated with a diagnosis of asthma and/or bronchiectasis a few years later, however, consequences into middle-age are unknown. OBJECTIVE: To investigate the relationship between childhood bronchitis and respiratory-related health outcomes in middle-age. DESIGN: Cohort study from age 7 to 53 years. SETTING: General population of European descent from Tasmania, Australia. PARTICIPANTS: 3202 participants of the age 53-year follow-up (mean age 53, range 51-55) of the Tasmanian Longitudinal Health Study cohort who were born in 1961 and first investigated at age 7 were included in our analysis. STATISTICAL METHODS: Multivariable linear and logistic regression. The association between parent reported childhood bronchitis up to age 7 and age 53-year lung conditions (n=3202) and lung function (n=2379) were investigated. RESULTS: Among 3202 participants, 47.5% had one or more episodes of childhood bronchitis, classified according to severity based on the number of episodes and duration as: 'non-recurrent bronchitis' (28.1%); 'recurrent non-protracted bronchitis' (18.1%) and 'recurrent-protracted bronchitis' (1.3%). Age 53 prevalence of doctor-diagnosed asthma and pneumonia (p-trend <0.001) and chronic bronchitis (p-trend=0.07) increased in accordance with childhood bronchitis severities. At age 53, 'recurrent-protracted bronchitis' (the most severe subgroup in childhood) was associated with doctor-diagnosed current asthma (OR 4.54, 95% CI 2.31 to 8.91) doctor-diagnosed pneumonia (OR=2.18 (95% CI 1.00 to 4.74)) and, paradoxically, increased transfer factor for carbon monoxide (z-score +0.51 SD (0.15-0.88)), when compared with no childhood bronchitis. CONCLUSION: In this cohort born in 1961, one or more episodes of childhood bronchitis was a frequent occurrence. 'Recurrent-protracted bronchitis', while uncommon, was especially linked to multiple respiratory outcomes almost five decades later, including asthma, pneumonia and raised lung gas transfer. These findings provide insights into the natural history of childhood 'bronchitis' into middle-age.

In vivo antihyperglycaemic and antihyperlipidemic activities and chemical constituents of Solanum anomalum.

Solanum anomalum is a plant used ethnomedically for the treatment of diabetes. The study was aimed to validate ethnomedical claims in rat model and identify the likely antidiabetic compounds. Leaf extract (70-210 mg/kg/day) and fractions (140 mg/kg/day) of S. anomalum were evaluated in hyperglycaemic rats induced using alloxan for effects on blood glucose, lipids and pancreas histology. Phytochemical characterisation of isolated compounds and their identification were performed using mass spectrometry and NMR spectroscopy. Bioinformatics tool was used to predict the possible protein targets of the identified bioactive compounds. The leaf extract/fractions on administration to diabetic rats caused significant lowering of fasting blood glucose of the diabetic rats during single dose study and on repeated administration of the extract. The hydroethanolic leaf extracts also enhanced glucose utilization capacity of the diabetic rats and caused significant lowering of glycosylated hemoglobin levels and elevation of insulin levels in the serum. Furthermore, triglycerides, LDL-cholesterol, and VLDL-cholesterol levels were lowered significantly, while HDL-cholesterol levels were also elevated in the treated diabetic rats. There was absence or few pathological signs in the treated hyperglycaemic rat pancreas compared to that present in the pancreas of control group. Diosgenin, 25(R)-diosgenin-3-O-α-L-rhamnopyranosyl-(1→4)-ß-D-glucopyranoside, uracil, thymine, 1-octacosanol, and octacosane were isolated and identified. Protein phosphatases along with secreted proteins are predicted to be the major targets of diosgenin and the diosgenin glycoside. These results suggest that the leaf extract/fractions of S. anomalum possess antidiabetic and antihyperlipidemic properties, offer protection to the pancreas and stimulate insulin secretion, which can be attributable to the activities of its phytochemical constituents.

Association between very to moderate preterm births, lung function deficits, and COPD at age 53 years: analysis of a prospective cohort study.

BACKGROUND: Prematurity has been linked to reduced lung function up to age 33 years, but its long-term effects on lung function and chronic obstructive pulmonary disease (COPD) are unknown. To address this question, we investigated associations between prematurity, lung function, and COPD in the sixth decade of life using data from the Tasmanian Longitudinal Health Study (TAHS). METHODS: Data were analysed from 1445 participants in the TAHS. Lung function was measured at 53 years of age. Gestational ages were very preterm (28 weeks to <32 weeks), moderate preterm (32 weeks to <34 weeks), late preterm (34 weeks to <37 weeks) and term (≥37 weeks). Linear and logistic regression models were fitted to investigate associations of prematurity with lung function measures (FEV1, forced vital capacity [FVC], FEV1/FVC ratio, forced expiratory flow at 25-75% of FVC [FEF25-75%], diffusing capacity for carbon monoxide [DLCO]) and COPD (post-bronchodilator FEV1/FVC less than the lower limit of normal), adjusting for sex, age, height, parental smoking during pregnancy, number of older siblings, maternal age at birth, and childhood socioeconomic status. Interactions with smoking and asthma were also investigated. RESULTS: Of 3565 individuals with available data on gestational age from the TAHS cohort, 1445 (41%) participants were included in this study, 740 (51%) of whom were female. Compared with term birth, very to moderate preterm birth was significantly associated with an increased risk of COPD at age 53 years (odds ratio 2·9 [95% CI 1·1-7·7]). Very-to-moderate preterm birth was also associated with lower post-bronchodilator FEV1/FVC ratio (beta-coefficient -2·9% [95% CI -4·9 to -0·81]), FEV1 (-190 mL [-339 to -40]), DLCO (-0·55 mmol/min/kPa [-0·97 to -0·13]), and FEF25-75% (-339 mL/s [-664 to -14]). The association between very-to-moderate preterm birth and FEV1/FVC ratio was only significant among smokers (pinteraction=0·0082). Similar findings were observed for moderate preterm birth when analysed as a separate group. Compared with term birth, late preterm birth was not associated with lower FEV1/FVC ratio or COPD. INTERPRETATION: This is the first study to investigate the effect of prematurity on lung function into middle-age. Data show that very-to-moderate prematurity is associated with obstructive lung function deficits including COPD well into the sixth decade of life and that this effect is compounded by personal smoking. FUNDING: National Health and Medical Research Council (NHMRC) of Australia, European Union's Horizon 2020, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, The Victorian, Queensland & Tasmanian Asthma Foundations, The Royal Hobart Hospital, Helen MacPherson Smith Trust, and GlaxoSmithKline.

Ten-year prediction model for post-bronchodilator airflow obstruction and early detection of COPD: development and validation in two middle-aged population-based cohorts.

BACKGROUND: Classifying individuals at high chronic obstructive pulmonary disease (COPD)-risk creates opportunities for early COPD detection and active intervention. OBJECTIVE: To develop and validate a statistical model to predict 10-year probabilities of COPD defined by post-bronchodilator airflow obstruction (post-BD-AO; forced expiratory volume in 1 s/forced vital capacity<5th percentile). SETTING: General Caucasian populations from Australia and Europe, 10 and 27 centres, respectively. PARTICIPANTS: For the development cohort, questionnaire data on respiratory symptoms, smoking, asthma, occupation and participant sex were from the Tasmanian Longitudinal Health Study (TAHS) participants at age 41-45 years (n=5729) who did not have self-reported COPD/emphysema at baseline but had post-BD spirometry and smoking status at age 51-55 years (n=2407). The validation cohort comprised participants from the European Community Respiratory Health Survey (ECRHS) II and III (n=5970), restricted to those of age 40-49 and 50-59 with complete questionnaire and spirometry/smoking data, respectively (n=1407). STATISTICAL METHOD: Risk-prediction models were developed using randomForest then externally validated. RESULTS: Area under the receiver operating characteristic curve (AUCROC) of the final model was 80.8% (95% CI 80.0% to 81.6%), sensitivity 80.3% (77.7% to 82.9%), specificity 69.1% (68.7% to 69.5%), positive predictive value (PPV) 11.1% (10.3% to 11.9%) and negative predictive value (NPV) 98.7% (98.5% to 98.9%). The external validation was fair (AUCROC 75.6%), with the PPV increasing to 17.9% and NPV still 97.5% for adults aged 40-49 years with ≥1 respiratory symptom. To illustrate the model output using hypothetical case scenarios, a 43-year-old female unskilled worker who smoked 20 cigarettes/day for 30 years had a 27% predicted probability for post-BD-AO at age 53 if she continued to smoke. The predicted risk was 42% if she had coexistent active asthma, but only 4.5% if she had quit after age 43. CONCLUSION: This novel and validated risk-prediction model could identify adults aged in their 40s at high 10-year COPD-risk in the general population with potential to facilitate active monitoring/intervention in predicted 'COPD cases' at a much earlier age.

Lung function trajectory and biomarkers in the Tasmanian Longitudinal Health Study.

BACKGROUND AND OBJECTIVE: Different lung function trajectories through life can lead to COPD in adulthood. This study investigated whether circulating levels of biomarkers can differentiate those with accelerated (AD) from normal decline (ND) trajectories. METHODS: The Tasmanian Longitudinal Health Study (TAHS) is a general population study that measured spirometry and followed up participants from ages 7 to 53 years. Based on their forced expiratory volume in 1 s (FEV1) trajectories from age 7 to 53 years, this analysis included those with COPD at age 53 years (60 with AD and 94 with ND) and controls (n=720) defined as never-smokers with an average FEV1 trajectory. Circulating levels of selected biomarkers determined at 53 and 45 years of age were compared between trajectories. RESULTS: Results showed that CC16 levels (an anti-inflammatory protein) were lower and C-reactive protein (CRP) (a pro-inflammatory marker) higher in the AD than in the ND trajectory. Higher CC16 levels were associated with a decreased risk of belonging to the AD trajectory (OR=0.79 (0.63-0.98) per unit increase) relative to ND trajectory. Higher CRP levels were associated with an increased risk of belonging to the AD trajectory (OR=1.07, 95% CI: 1.00-1.13, per unit increase). Levels of CC16 (area under the curve (AUC)=0.69, 95% CI: 0.56-0.81, p=0.002), CRP (AUC=0.63, 95% CI: 0.53-0.72, p=0.01) and the combination of both (AUC=0.72, 95% CI: 0.60-0.83, p<0.001) were able to discriminate between the AD and ND trajectories. Other quantified biomarkers (interleukin (IL)-4, IL-5, IL-6, IL-10 and tumour necrosis factor-α (TNF-α)) were not significantly different between AD, ND and controls. CONCLUSIONS: Circulating levels of CRP and CC16 measured in late adulthood identify different lung function trajectories (AD versus ND) leading to COPD at age 53 years.

Maternal Particulate Matter Exposure Impairs Lung Health and Is Associated with Mitochondrial Damage.

Relatively little is known about the transgenerational effects of chronic maternal exposure to low-level traffic-related air pollution (TRAP) on the offspring lung health, nor are the effects of removing such exposure before pregnancy. Female BALB/c mice were exposed to PM2.5 (PM2.5, 5 µg/day) for 6 weeks before mating and during gestation and lactation; in a subgroup, PM was removed when mating started to model mothers moving to cleaner areas during pregnancy to protect their unborn child (Pre-exposure). Lung pathology was characterised in both dams and offspring. A subcohort of female offspring was also exposed to ovalbumin to model allergic airways disease. PM2.5 and Pre-exposure dams exhibited airways hyper-responsiveness (AHR) with mucus hypersecretion, increased mitochondrial reactive oxygen species (ROS) and mitochondrial dysfunction in the lungs. Female offspring from PM2.5 and Pre-exposure dams displayed AHR with increased lung inflammation and mitochondrial ROS production, while males only displayed increased lung inflammation. After the ovalbumin challenge, AHR was increased in female offspring from PM2.5 dams compared with those from control dams. Using an in vitro model, the mitochondria-targeted antioxidant MitoQ reversed mitochondrial dysfunction by PM stimulation, suggesting that the lung pathology in offspring is driven by dysfunctional mitochondria. In conclusion, chronic exposure to low doses of PM2.5 exerted transgenerational impairment on lung health.

Isolation and characterization of bioactive xanthones from Hippocratea africana (Willd.)Loes.ex Engl. (Celastraceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Hippocratea africana root is used in African folk medicine for the treatment of several ailments, including pain and inflammation. AIM OF THE STUDY: To isolate anti-inflammatory and analgesic compounds from the roots of H. africana, with accompanying antioxidant potentials. MATERIALS AND METHODS: Dichloromethane, ethyl acetate, and aqueous fractions of H. africana roots, and isolated compounds from the bioactive ethyl acetate fraction were evaluated for anti-inflammatory and analgesic activities using the xylene induced oedema in mice and thermal induced pain models, respectively. The antioxidant potentials of isolated compounds were tested in 2,2-diphenyl-1-picryhydrazyl radical and ferric reducing antioxidant power assays. Structures were elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR experiments, ionization mass spectrometry, and comparison with literature data. RESULTS: Isoathyriol (1,3,7-trihydroxy-6-methoxyxanthone) and norathyriol (1,3,6,7-tetrahydroxyxanthone) were isolated from the potent anti-inflammatory and analgesic ethyl acetate fraction of H. africana roots. Isoathyriol and norathyriol demonstrated good anti-inflammatory, analgesic, and antioxidant properties compared with the standards used in each assay. CONCLUSIONS: This study substantiates the use of H. africana root extract in the alleviation of inflammation and pain, and reports the characterization of secondary metabolites in H. africana and for the first time the presence of xanthones in Hippocratea genus.

Association between ambient air pollution and development and persistence of atopic and non-atopic eczema in a cohort of adults.

BACKGROUND: There is limited information on risk factors for eczema in adults. Recent evidence suggests that air pollution may be associated with increased incidence of eczema in adults. We aimed to assess this possible association. METHODS: Ambient air pollution exposures (distance from a major road, nitrogen dioxide [NO2 ], fine particulate matter with an aerodynamic diameter ≤2.5 µm [PM2.5 ]) were assessed for the residential address of Tasmanian Longitudinal Health Study participants at ages 43 and 53 years. Eczema incidence (onset after age 43 years), prevalence (at 53 years), and persistence were assessed from surveys, while IgE sensitization was assessed using skin prick tests. The presence or absence of eczema and sensitization was classified into four groups: no atopy or eczema, atopy alone, non-atopic eczema, and atopic eczema. Adjusted logistic and multinomial regression models were fitted to estimate associations between ambient air pollution and eczema, and interaction by sex was assessed. RESULTS: Of 3153 participants in both follow-ups, 2369 had valid skin prick tests. For males, a 2.3 ppb increase in baselineNO2 was associated with increased odds of prevalent eczema (OR = 1.15 [95% CI 0.98-1.36]) and prevalent atopic eczema (OR = 1.26 [1.00-1.59]). These associations were not seen in females (p for interaction = 0.08, <0.01). For both sexes, a 1.6 µg/m3 increase in PM2.5 exposure at follow-up was associated with increased odds of aeroallergen sensitization (OR = 1.15 [1.03-1.30]). CONCLUSION: Increased exposure to residential ambient air pollutants was associated with an increased odds of eczema, only in males, and aeroallergen sensitization in both genders.

Bronchodilator reversibility as a diagnostic test for adult asthma: findings from the population-based Tasmanian Longitudinal Health Study.

Bronchodilator reversibility (BDR) is often used as a diagnostic test for adult asthma. However, there has been limited assessment of its diagnostic utility. We aimed to determine the discriminatory accuracy of common BDR cut-offs in the context of current asthma and asthma-COPD overlap (ACO) in a middle-aged community sample. The Tasmanian Longitudinal Health Study is a population-based cohort first studied in 1968 (n=8583). In 2012, participants completed respiratory questionnaires and spirometry (n=3609; mean age 53 years). Receiver operating characteristic (ROC) curves were fitted for current asthma and ACO using continuous BDR measurements. Diagnostic parameters were calculated for different categorical cut-offs. Area under the ROC curve (AUC) was highest when BDR was expressed as change in forced expiratory volume in 1 s (FEV1) as a percentage of initial FEV1, as compared with predicted FEV1. The corresponding AUC was 59% (95% CI 54-64%) for current asthma and 87% (95% CI 81-93%) for ACO. Of the categorical cut-offs examined, the European Respiratory Society/American Thoracic Society threshold (≥12% from baseline and ≥200 mL) was assessed as providing the best balance between positive and negative likelihood ratios (LR+ and LR-, respectively), with corresponding sensitivities and specificities of 9% and 97%, respectively, for current asthma (LR+ 3.26, LR- 0.93), and 47% and 97%, respectively, for ACO (LR+ 16.05, LR- 0.55). With a threshold of ≥12% and ≥200 mL from baseline, a positive BDR test provided a clinically meaningful change in the post-test probability of disease, whereas a negative test did not. BDR was more useful as a diagnostic test in those with co-existent post-bronchodilator airflow obstruction (ACO).

Does the use of inhaled corticosteroids in asthma benefit lung function in the long-term? A systematic review and meta-analysis.

While asthma is known to be associated with an increased risk of progressive lung function impairments and fixed airflow obstruction, there is ongoing debate on whether inhaled corticosteroids (ICS) modify these long-term risks. Searches were performed of the PubMed, Embase and CENTRAL databases up to 22 July 2019 for studies with follow-up ≥1 year that investigated the effects of maintenance ICS on changes in lung function in asthma.Inclusion criteria were met by 13 randomised controlled trials (RCTs) (n=11 678) and 11 observational studies (n=3720). Median (interquartile range) follow-up was 1.0 (1-4) and 8.4 (3-28) years, respectively. In the RCTs, predominantly in individuals with mild asthma, ICS use was associated with improved pre-bronchodilator (BD) forced expiratory volume in 1 s (FEV1) across all age groups (2.22% predicted (95% CI 1.32-3.12), n=8332), with similar estimates of strength in association for children and adults. Improvements in post-BD FEV1 were observed in adults (1.54% (0.87-2.21), n=3970), but not in children (0.20% (-0.49-0.90), n=3924) (subgroup difference, p=0.006). Estimates were similar between smokers and nonsmokers. There were no RCT data on incidence of fixed airflow obstruction. In the observational studies, ICS use was associated with improved pre-BD FEV1 in children and adults. There were limited observational data for post-BD outcomes.In patients with mild asthma, maintenance ICS are associated with modest, age-dependent improvements in long-term lung function, representing an added benefit to the broader clinical actions of ICS in asthma. There is currently insufficient evidence to determine whether treatment reduces incidence of fixed airflow obstruction in later life.

Severe asthma assessment, management and the organisation of care in Australia and New Zealand: expert forum roundtable meetings.

Severe asthma imposes a significant burden on individuals, families and the healthcare system. Treatment is complex, due to disease heterogeneity, comorbidities and complexity in care pathways. New approaches and treatments improve health outcomes for people with severe asthma. However, emerging multidimensional and targeted treatment strategies require a reorganisation of asthma care. Consensus is required on how reorganisation should occur and what areas require further research. The Centre of Excellence in Severe Asthma convened three forums between 2015 and 2018, hosting experts from Australia, New Zealand and the UK. The forums were complemented by a survey of clinicians involved in the management of people with severe asthma. We sought to: (i) identify areas of consensus among experts; (ii) define activities and resources required for the implementation of findings into practice; and (iii) identify specific priority areas for future research. Discussions identified areas of unmet need including assessment and diagnosis of severe asthma, models of care and treatment pathways, add-on treatment approaches and patient perspectives. We recommend development of education and training activities, clinical resources and standards of care documents, increased stakeholder engagement and public awareness campaigns and improved access to infrastructure and funding. Further, we propose specific future research to inform clinical decision-making and develop novel therapies. A concerted effort is required from all stakeholders (including patients, healthcare professionals and organisations and government) to integrate new evidence-based practices into clinical care and to advance research to resolve questions relevant to improving outcomes for people with severe asthma.

Exposure to household air pollution over 10†years is related to asthma and lung function decline.

INTRODUCTION: We investigated if long-term household air pollution (HAP) is associated with asthma and lung function decline in middle-aged adults, and whether these associations were modified by glutathione S-transferase (GST) gene variants, ventilation and atopy. MATERIALS AND METHODS: Prospective data on HAP (heating, cooking, mould and smoking) and asthma were collected in the Tasmanian Longitudinal Health Study (TAHS) at mean ages 43 and 53 years (n=3314). Subsamples had data on lung function (n=897) and GST gene polymorphisms (n=928). Latent class analysis was used to characterise longitudinal patterns of exposure. Regression models assessed associations and interactions. RESULTS: We identified seven longitudinal HAP profiles. Of these, three were associated with persistent asthma, greater lung function decline and % reversibility by age 53 years compared with the "Least exposed" reference profile for those who used reverse-cycle air conditioning, electric cooking and no smoking. The "All gas" (OR 2.64, 95% CI 1.22-5.70), "Wood heating/smoking" (OR 2.71, 95% CI 1.21-6.05) and "Wood heating/gas cooking" (OR 2.60, 95% CI 1.11-6.11) profiles were associated with persistent asthma, as well as greater lung function decline and % reversibility. Participants with the GSTP1 Ile/Ile genotype were at a higher risk of asthma or greater lung function decline when exposed compared with other genotypes. Exhaust fan use and opening windows frequently may reduce the adverse effects of HAP produced by combustion heating and cooking on current asthma, presumably through increasing ventilation. CONCLUSIONS: Exposures to wood heating, gas cooking and heating, and tobacco smoke over 10 years increased the risks of persistent asthma, lung function decline and % reversibility, with evidence of interaction by GST genes and ventilation.