Prevalence and burden of difficult-to-treat and severe asthma in Australia: A national population survey.

BACKGROUND AND OBJECTIVE: Most evidence about difficult-to-treat and severe asthma (DTTA) comes from clinical trials and registries. We aimed to identify people with DTTA from a large nationally representative asthma population and describe their characteristics and healthcare utilization compared with people whose asthma was not 'difficult-to-treat'. METHODS: We conducted a cross-sectional survey of Australians aged ≥18 years with current asthma from large web-based survey panels. Enrolment was stratified by gender, age-group and state/territory based on national population data for people with asthma. Difficult-to-treat or severe asthma was defined by poor symptom control, exacerbations and/or oral corticosteroid/biologic use despite medium/high-dose inhaled therapy. Outcomes included exacerbations, healthcare utilization, multimorbidity, quality of life and coronavirus disease of 2019 (COVID-19)-related behaviour. Weighted data were analysed using SAS version 9.4. RESULTS: The survey was conducted in February-March 2021. The weighted sample comprised 6048 adults with current asthma (average age 47.3 ± SD 18.1 years, 59.9% female), with 1313 (21.7%) satisfying ≥1 DTTA criteria. Of these, 50.4% had very poorly controlled symptoms (Asthma Control Test ≤15), 36.2% were current smokers, and 85.4% had ≥1 additional chronic condition, most commonly anxiety/depression. More than twice as many participants with DTTA versus non-DTTA had ≥1 urgent general practitioner (GP) visit (61.4% vs. 27.5%, OR 4.8 [4.2-5.5, p < 0.0001]), or ≥1 emergency room visit (41.9% vs. 17.9%, OR 3.8 [3.3-4.4, p < 0.0001]) in the previous 12 months. CONCLUSION: Our findings emphasize the burden of uncontrolled symptoms, current smoking, multimorbidity and healthcare utilization in people with DTTA in the community, who may be under-represented in registries or clinical trials.

Contribution of obesity to breathlessness in a large nationally representative sample of Australian adults.

BACKGROUND AND OBJECTIVE: Breathlessness is prevalent and associated with medical consequences. Obesity is related to breathlessness. However, the magnitude of its contribution has not been clearly documented. This investigation aimed to determine the contribution of obesity to breathlessness by estimating the population attributable fraction (PAF) in a representative sample of Australian adults. METHODS: A cross-sectional, nationally representative survey of Australian residents aged ≥18 years was conducted in October 2019. Breathlessness was defined as modified Medical Research Council (mMRC) dyspnoea scale grade ≥2. BMI was calculated from self-reported height and weight. Adjusted relative risks (aRRs) were estimated using a generalized linear model with Poisson distribution, adjusted for age group and/or participant-reported diagnosed illnesses. Adjusted PAFs were estimated using aRR and obesity prevalence in Australian adults. RESULTS: Among those who completed the National Breathlessness Survey, 9769 participants (51.4% female) were included in the analysis; 28.1% of participants were obese. The prevalence of breathlessness was 9.54%. The aRR of obesity for breathlessness was 2.04, adjusted for age. Adjusting for various co-morbid conditions, the aRR was slightly attenuated to around 1.85-1.98. The PAF, adjusted only for age, was 24.6% (95% CI 20.1-29.1) and after further adjustment for co-morbid conditions, the PAF ranged from 21.1% to 23.6%. Obesity accounted for a higher proportion of breathlessness in women than in men. CONCLUSION: Our results demonstrate that obesity accounts for around a quarter of breathlessness symptoms in Australian adults. This has important implications for health policy in light of the global trend in increasing obesity.

Qualitative validation of the modified Medical Research Council (mMRC) dyspnoea scale as a patient-reported measure of breathlessness severity.

INTRODUCTION: The modified Medical Research Council (mMRC) dyspnoea scale is a measure of breathlessness severity recommended by guidelines and utilised as an inclusion criterion or endpoint for clinical trials. No studies have been conducted to validate the categorical descriptors against the dyspnoea severity grade. METHODS: This study utilised cognitive interviews (Think Aloud method) to assess the content validity of the mMRC scale among 16 participants (13 with cardiac/respiratory disease). Participants were recruited to achieve representation across a variety of demographic factors. Interviews were conducted remotely via video conferencing and participants were presented with all 5 mMRC descriptors on screen in random order then asked to rank the statements "in order from the best breathing to the worst breathing". RESULTS: Mean age of participants was 57 years (range 22-84 years). Eleven had multimorbidity (≥2 comorbidities) including COPD, asthma, lung cancer, lung infection, interstitial lung disease, heart failure, depression, and anxiety. Length of time with breathlessness ranged between 2 weeks and >25 years. The median rank of the mMRC grade descriptors was concordant for mMRC grades 0, 1 and 4 but not grades 2 and 3. Even so, substantial heterogeneity was found in the distribution of responses for mMRC grade 0. CONCLUSION: Our study found substantial heterogeneity in participant grading of the mMRC descriptors, particularly for grades 0, 2 and 3, indicating that mMRC might not be a good discriminator of difference or change in dyspnoea severity. This study demonstrates the importance of content validation even for long-established PROs like mMRC.

Lower workforce participation is associated with more severe persisting breathlessness.

BACKGROUND: Not being able to work has negative health, social and financial consequences. Persisting breathlessness is prevalent in working-aged people. Is it associated with lower workforce participation? This study, using the South Australian Health Omnibus, aimed to explore associations between paid workforce participation and persisting breathlessness intensity, and economic impacts on income in people of working age. METHODS: This cross-sectional study conducted face-to-face interviews with a random sample of adults in South Australia (n = 8916). Questions included key demographic data, workforce participation and the presence and intensity of persisting breathlessness. Data from working-aged respondents (20-65 years of age) were standardised to the census for regression analyses. Work was coded to paid full- or part-time work or 'other'. Persisting breathlessness (more than three of the last six months) used the modified Medical Research Council breathlessness scale (aggregated to 0, 1, 2-4). Opportunity cost valuations compared annual income foregone by persisting breathlessness severity. RESULTS: Of people interviewed, 6,608 were working-aged (49.9% male; 67.5% had post-secondary qualifications; 70.9% were in paid full- or part-time work; and 1.7% had mMRC score 2-4). Workforce participation dropped in working aged people with increasing breathlessness: mMRC 0, 70.6%; mMRC 1, 51.7%; mMRC 2-4, 20.3%. In the regression model, people with the most severe breathlessness were much less likely to work (OR 0.14; 95% CI 0.09, 0.22). Annual income foregone by people with persisting breathlessness was AU$10.7 billion (AU$9.1b for full-time and AU$1.6b for part-time work; range AU$5.9b, AU$49.7b). CONCLUSION: Worsening persisting breathlessness is associated with lower workforce participation with direct financial consequences, greatest for older males.

Relationship between life-time exposure to ambient fine particulate matter and carotid artery intima-media thickness in Australian children aged 11-12 years.

Long-term exposure to air pollutants, especially particulates, in adulthood is related to cardiovascular diseases and vascular markers of atherosclerosis. However, whether vascular changes in children is related to exposure to air pollutants remains unknown. This study examined whether childhood exposure to air pollutants was related to a marker of cardiovascular risk, carotid intima-media thickness (CIMT) in children aged 11-12 years old. Longitudinal Study of Australian Children (LSAC) recruited parents and their children born in 2003-4. Among the participants, CheckPoint examination was conducted when the children were 11-12 years old. Ultrasound of the right carotid artery was performed using standardized protocols. Average and maximum far-wall CIMT, carotid artery distensibility, and elasticity were quantified using semiautomated software. Annual and life-time exposure to air pollutants was estimated using satellite-based land-use regression by residential postcodes. A total of 1063 children (50.4% girls) with CIMT data, serum cholesterol, and modeled estimates of NO2 and PM2.5 exposure for the period 2003 to 2015 were included. The average and maximum CIMT, carotid distensibility, and elasticity were 497 µm (standard deviation, SD 58), 580 µm (SD 44), 17.4% (SD 3.2), and 0.48%/mmHg (SD 0.09), respectively. The life-time average concentrations of PM2.5 and NO2 were 6.4 µg/m3 (SD 1.4) and 6.4 ppb (SD 2.4), respectively. Both average and maximum CIMT were significantly associated with average ambient PM2.5 concentration (average CIMT: +5.5 µm per µg/m3, 95% confidence interval, CI 2.4 to 8.5, and maximum CIMT: +4.9 µm per µg/m3, CI 2.3 to 7.6), estimated using linear regression, adjusting for potential confounders. CIMT was not significantly related to NO2 exposure. Carotid artery diameter, distensibility, and elasticity were not significantly associated with air pollutants. We conclude that life-time exposure to low levels of PM2.5 in children might have measurable adverse impacts on vascular structure by age 11-12 years.

Prevalence and burden of breathlessness in Australian adults: The National Breathlessness Survey-a cross-sectional web-based population survey.

BACKGROUND AND OBJECTIVE: Chronic respiratory symptoms (in particular, breathlessness and cough) can cause physical, social and emotional distress, and may indicate the presence of an underlying disease that presages future poor health outcomes. Our aim was to investigate the burden of breathlessness in Australian adults, including breathlessness that may be undiagnosed, unlabelled or untreated. METHODS: The National Breathlessness Survey was a cross-sectional, web-based survey conducted in October 2019. Australian adults were randomly selected from a large web-based survey panel with recruitment stratified by age-group, gender and state of residence according to national population data. The main outcome measures were modified Medical Research Council (mMRC) dyspnoea scale, EuroQol visual analog scale, Dyspnoea-12 score and 4-item Patient Health Questionnaire (PHQ-4). RESULTS: Among all respondents (n = 10,072; 51.1% female; median age group 40-49 years), 9.5% reported clinically important breathlessness (mMRC dyspnoea grade ≥ 2, 2 = 'I walk slower than people of the same age on the level because of breathlessness or have to stop for breath when walking at my own pace on the level'). Among those with clinically important breathlessness, 49.1% rated their general health as fair or poor and 44.2% had at least moderate depression or anxiety symptoms (PHQ ≥ 6) but over half (50.8%) did not report a current respiratory or heart condition diagnosis. CONCLUSION: Breathlessness is common among Australian adults, and is associated with a substantial burden of ill health, including among people without a diagnosed respiratory or heart condition. The extent of underdiagnosis of these conditions or alternative causes of breathlessness requires further investigation.

Inappropriate prescribing of inhaled corticosteroids: are they being prescribed for respiratory tract infections? A retrospective cohort study.

BACKGROUND: Guidelines recommend regular use of inhaled corticosteroid (ICS)-containing medications for all patients with persistent asthma and those with moderate to severe chronic obstructive pulmonary disease. It is important to identify indicators of inappropriate prescribing. AIMS: To test the hypothesis that ICS are prescribed for the management of respiratory infections in some patients lacking evidence of chronic airways disease. METHODS: Medication dispensing data were obtained from the Australian national Pharmaceutical Benefits Scheme (PBS) for concessional patients dispensed any respiratory medications during 2008. We identified people dispensed only one ICS-containing medication and no other respiratory medications in a year, who were therefore unlikely to have chronic airways disease, and calculated the proportion who were co-dispensed oral antibiotics. RESULTS: In 2008, 43.6% of the 115,763 patients who were dispensed one-off ICS were co-dispensed oral antibiotics. Co-dispensing was seasonal, with a large peak in winter months. The most commonly co-dispensed ICS among adults were moderate/high doses of combination therapy, while lower doses of ICS alone were co-dispensed among children. In this cohort, one-off ICS co-dispensed with oral antibiotics cost the government $2.7 million in 2008. CONCLUSIONS: In Australia, many people who receive one-off prescriptions for ICS-containing medications do not appear to have airways disease. In this context, the high rate of co-dispensing with antibiotics suggests that ICS are often inappropriately prescribed for the management of symptoms of respiratory infection. Interventions are required to improve the quality of prescribing of ICS and the management of respiratory infections in clinical practice.

Cost is a major barrier to the use of inhaled corticosteroids for obstructive lung disease.

OBJECTIVE: To examine the effect of the level of patient copayment on the rate of purchase of inhaled corticosteroids (ICS) by patients with obstructive lung disease. DESIGN AND SETTING: Cross-sectional study of records of all prescriptions for ICS dispensed to general and concessional beneficiaries aged 15 years or over in the period January 2003 to December 2006. Data were obtained from the Pharmaceutical Benefits Scheme, which subsidises medication costs for all Australians. MAIN OUTCOME MEASURES: The number of prescriptions for ICS dispensed to government concession card holders compared with the number dispensed to general beneficiaries, expressed as a rate ratio. RESULTS: ICS prescriptions were dispensed to over 1.6 million people during the study period. Concession card holders were dispensed ICS prescriptions at a higher rate than general beneficiaries, both overall (43.7 v 9.1 ICS prescriptions per 100 person-years) and in all population subgroups. After adjusting for age, sex, remoteness category and socioeconomic status, people holding a concession card were dispensed over 2.5 times the number of ICS prescriptions (alone or in combination with a long-acting beta(2)-agonist) compared with general beneficiaries. Similar patterns were seen after adjusting for differences between the two groups in the prevalence of obstructive lung disease. CONCLUSIONS: As the patient copayment for general beneficiaries is over six times higher than for concession card holders, our findings imply that cost is a barrier to the purchase of ICS prescriptions for obstructive lung disease, independent of socioeconomic status.

Asthma in older adults: a holistic, person-centred and problem-oriented approach.

Regardless of how obstructive lung disease is labelled, targeting treatment to components of the problem is the best solution.

The Halogen assay--a new technique for measuring airborne allergen.

The Halogen assay is a new technique for measuring airborne allergen. The assay is unique in that it is capable of analyzing allergens and particles together, combining the advantages of morphological approaches and immunoassay. The Halogen assay allows direct observation of the particles that carry the allergen as well as being capable of identifying all the allergen sources an individual is exposed and sensitized to. The assay is sensitive because the extracted allergen is bound to the membrane at a high local concentration within the minute area around each particle and so is easily detected by immunostaining. It is therefore easy to detect few pollen grains. The Halogen method supersedes other methods commonly used to identify allergens as it is capable of identifying airborne particles that are allergen sources.

Trends in hospitalizations for anaphylaxis, angioedema, and urticaria in Australia, 1993-1994 to 2004-2005.

BACKGROUND: Recent investigations in developed countries have found marked increases in the prevalence of allergic conditions. OBJECTIVE: We sought to examine recent time trends in the prevalence of anaphylaxis, angioedema, and urticaria by describing trends and age and sex differentials in hospitalizations for these conditions in Australia. METHODS: Data on hospital admissions and deaths for anaphylaxis, angioedema, and urticaria were extracted for the periods 1993-1994 to 2004-2005 and 1997-2004, respectively. For hospital admissions, age-standardized rates were calculated. Time trends and sex differences were quantified by using negative binomial models. RESULTS: During the study period, there was a continuous increase in the rate of hospital admissions for angioedema (3.0% per year), urticaria (5.7% per year), and, most notably, anaphylaxis (8.8% per year). There was a particularly steep increase in the incidence of hospitalization for food-related anaphylaxis among children aged less than 5 years. Admissions for non-food-related anaphylaxis occurred predominantly in adults, particularly those more than 35 years of age. Among children, admission rates were higher in boys, but the sex difference was reversed among adults. Over an 8-year period, there were 106 deaths associated with anaphylaxis or angioedema. CONCLUSION: Hospitalization rates for allergic conditions are on the increase, but the nature and causative factors differ between adults and children. The relation of these changes to those in the prevalence of specific allergen sensitization in the community requires further investigation in population studies. CLINICAL IMPLICATIONS: Among older persons, angioedema is becoming an increasing problem. Among children, hospitalization because of food-induced anaphylaxis is a growing concern.

A nationwide perspective on asthma in older Australians.

WHAT WE NEED TO KNOW: What is the prevalence of impaired lung function among older people in Australia? How can we differentiate between asthma and other causes of breathlessness in population-based health surveys of older people? What are the effects of ageing on people with asthma? WHAT WE NEED TO DO: Improve existing survey measures and accuracy of diagnosis. Incorporate measures of spirometric function into health surveys of representative samples of the general population. Use spirometry in the diagnostic work-up of older patients with dyspnoea.

The burden of asthma in children: an Australian perspective.

The burden of asthma among children is high in Australia compared with many other countries. Recent data show that 14-16% of children report a diagnosis of asthma that remains a problem. Boys, children under the age of 5 years and urban indigenous children experience a greater burden of asthma than other children. More than one-third of children with asthma have sleep disturbance due to the illness and 60% have missed school and/or experienced other restrictions in their activities due to the disease. Despite this, there is continuing evidence of under-utilisation of effective treatment for the disease. Asthma is a major cause of healthcare utilisation among children. Since the early 1990s, there has been a decline in both hospitalisation rates and general practitioner consultation rates for asthma among children. It remains to be seen whether this favourable trend will continue and extend into the adult age range.

Inhaled latex allergen (Hev b 1).

BACKGROUND: IgE-mediated responses to natural rubber latex allergens have become a major health problem among recognized risk groups. OBJECTIVE: The purpose of this investigation was to measure the amounts of Hevea brasiliensis latex allergen (Hev b 1) inhaled and deposited on surfaces when latex or vinyl gloves were worn and compare the results with the conventional measures (breathing zone samplers) of occupational exposure. METHODS: Hev b 1 exposure was measured by nasal sampling and breathing zone sampling. Latex allergen exposure was generated by having each subject don a pair of powdered latex examination gloves and continuing his or her normal daily activity for 30 minutes. By means of adhesive tape, surface dust samples were collected from the surfaces of gloves, the subject's hands, and work areas. Sampling was performed with subjects wearing no gloves, subjects wearing powdered vinyl gloves, subjects wearing powdered latex gloves, and nearby colleagues wearing latex gloves. All samples were assayed through use of the HALOgen assay (Inhalix, Sydney, Australia) with a Hev b 1-specific mAb. Particles transporting latex allergen were identified by a surrounding immunostain halo, and these were quantified and reported as total numbers of particles inhaled, airborne, or found on surface areas evaluated. RESULTS: Study subjects inhaled 26 times more allergen when powdered latex gloves were worn than under the "no glove" and powdered vinyl glove conditions. During the same period, Hev b 1 particle levels measured in the ambient air through use of the breathing zone sampler increased by 24-fold. The median numbers of particles carrying Hev b 1 allergen per square centimeter on the surface of the hands after the wearing of latex and vinyl gloves were 1964 and 5, respectively. Latex allergen was physically associated both with cornstarch granules and with larger dust particles having a darker, more irregular appearance. CONCLUSION: In a laboratory where gloves are worn for protection, the use of latex gloves resulted in a 26-fold increase in inhaled latex allergen over background levels measured while vinyl gloves were worn as controls. Low levels of latex exposure also occurred when vinyl gloves or no gloves were worn; the reasons for this are under investigation.