Issue 2 - "Update on adverse respiratory effects of indoor air pollution". Part 2): Indoor air pollution and respiratory diseases: Perspectives from Italy and some other GARD countries.

OBJECTIVE: to synthesize the Italian epidemiological contribution to knowledge on indoor pollution respiratory impact, and to analyze the perspective of some GARD countries on the health effects of indoor air pollution. RESULTS: Italian epidemiological analytical studies confirmed a strong relationship between indoor air pollution and health in general population. Environmental tobacco smoke, biomass (wood/coal) fuel for cooking/heating and indoor allergens (house dust mites, cat and dog dander, mold/damp) are the most relevant indoor pollution sources and are related to respiratory and allergic symptoms/diseases in Italy and in other GARD countries such as Mexico, Brazil, Vietnam, India, Nepal and Kyrgyzstan. Community-based global health collaborations are working to improve prevention, diagnosis and care of respiratory diseases around the world, specially in low- and middle-income countries, through research and education. CONCLUSIONS: in the last thirty years, the scientific evidence produced on respiratory health effects of indoor air pollution has been extensive, but the necessity to empower the synergies between scientific community and local administrations remains a challenge to address in order to implement effective interventions. Based on abundant evidence of indoor pollution health effect, WHO, scientific societies, patient organizations and other members of the health community should work together to pursue the GARD vision of "a world where all people breathe freely" and encourage policy makers to increase their engagement in advocacy for clean air.

Association of coronary calcification with prognosis of Covid-19 patients without known heart disease.

Risk factors that determine the severity of Covid-19 have not been fully elucidated. The aim of this study was to evaluate the role of coronary artery calcification (CAC) as a risk factor for death or mechanical ventilation (MV) of patients without known heart disease infected with Covid-19. We analyzed 283 consecutive in-patients with acute respiratory symptoms with chest computed tomography (chest-CT), without previous heart disease, and criteria for Covid-19 (RT-PCR positive and/or typical clinical and chest-CT findings). CAC was classified by the number of coronary segments affected as absent (0), mild (1-3), and severe calcification (more than 3). The association between CAC, CAC severity, and death or MV due to severe respiratory failure was assessed by logistic regression. The mean age was 58.7±15.7 years and 54.1% were men. Patients with CAC were older, more likely to have hypertension, and less likely to be obese. CAC was present in 75 patients (26.5%), of which 42 had a mild calcification and 33 had severe calcification, and was associated with death (OR=2.35, 95%CI: 1.01-5.48) or MV (OR=2.72, 95%CI: 1.20-6.20) adjusted for multiple confounders, with significant and increased odds ratio for the severe form of CAC (death: OR=3.70, 95%CI: 1.20-11.42; MV: OR=3.30, 95%CI: 1.09-9.95). We concluded that CAC was an independent risk factor for death or MV in Covid-19 patients without previous heart disease, particularly for those with severe calcification. CAC can be easily visualized on common chest-CT, widely used in evaluation of moderate to severe Covid-19.

Association of coronary calcification with prognosis of Covid-19 patients without known heart disease

Risk factors that determine the severity of Covid-19 have not been fully elucidated. The aim of this study was to evaluate the role of coronary artery calcification (CAC) as a risk factor for death or mechanical ventilation (MV) of patients without known heart disease infected with Covid-19. We analyzed 283 consecutive in-patients with acute respiratory symptoms with chest computed tomography (chest-CT), without previous heart disease, and criteria for Covid-19 (RT-PCR positive and/or typical clinical and chest-CT findings). CAC was classified by the number of coronary segments affected as absent (0), mild (1-3), and severe calcification (more than 3). The association between CAC, CAC severity, and death or MV due to severe respiratory failure was assessed by logistic regression. The mean age was 58.7±15.7 years and 54.1% were men. Patients with CAC were older, more likely to have hypertension, and less likely to be obese. CAC was present in 75 patients (26.5%), of which 42 had a mild calcification and 33 had severe calcification, and was associated with death (OR=2.35, 95%CI: 1.01-5.48) or MV (OR=2.72, 95%CI: 1.20-6.20) adjusted for multiple confounders, with significant and increased odds ratio for the severe form of CAC (death: OR=3.70, 95%CI: 1.20-11.42; MV: OR=3.30, 95%CI: 1.09-9.95). We concluded that CAC was an independent risk factor for death or MV in Covid-19 patients without previous heart disease, particularly for those with severe calcification. CAC can be easily visualized on common chest-CT, widely used in evaluation of moderate to severe Covid-19.

Longitudinal trends in clinical characteristics and lung function of patients with severe asthma under treatment in Brazil.

BACKGROUND: The structural changes of the respiratory system related to ageing determine lung function decline in healthy subjects after 25 years of age. An annual reduction of 25 ml in Forced Expiratory Volume in 1 s (FEV1) is expected. We aimed to describe the longitudinal lung function variation of subjects with severe asthma receiving appropriate treatment. METHODS: Consecutive patients enrolled in a Brazilian reference clinic between 2003 and 2006 were invited to participate. The study participants were followed up for a median of 8 years, and were evaluated with spirometry in three distinct occasions (V0, V1 and V8), at least. At V0, upon enrollment, subjects with previous severe untreated asthma were evaluated by a specialist, had their health resource utilization in the last 12 months recorded, and performed spirometry. In V1, 1 year after V0, under proper management, subjects repeated the procedures and answered the Asthma Control Questionnaire (ACQ) and the Asthma Quality of Life Questionnaire (AQLQ). In the last study visit (V8), 7 years after V1, all patients underwent a pre and post-broncodilator (postBD) spirometry, skin prick test for aeroallergens, answered the ACQ and the AQLQ and had another interview with the specialist. RESULTS: Two hundred thirty-four subjects were followed up between V0 and V8. A comparison between spirometries of V1 and V8, after the initial improvement has supposedly reached a plateau, shows that the FEV1 and FVC declined significantly both in absolute and percent of predicted values. FEV1postBD did not change significantly between V0 and V1, but declined by -27.1 (-51.1-1.4) ml/yr between V1 and V8. CONCLUSIONS: Currently available treatment with a combination of inhaled corticosteroids and LABA may not be sufficient to prevent lung function decline in subjects with severe asthma.

Polymorphisms in IL10 are associated with total Immunoglobulin E levels and Schistosoma mansoni infection intensity in a Brazilian population.

Interleukin (IL)-10 is a regulatory cytokine of the helper T cell type 2 (TH2) pathway, which underlies both the host defense to helminthic infection and atopic diseases, including asthma. Although IL10 promoter polymorphisms are associated with increased atopy risk, IL10 variation has not been thoroughly explored in schistosomiasis-endemic populations. Three atopy-related IL10 promoter polymorphisms (rs1800896, rs1800871 and rs1800872), complemented by six tagging single-nucleotide polymorphisms (SNPs), were genotyped in 812 individuals in 318 nuclear families from a schistosomiasis-endemic area in Brazil. Associations between markers and total serum Immunoglobulin E (tIgE) levels, indicating non-specific activation of the TH2 pathway, and Schistosoma mansoni fecal egg counts, indicating burden of infection reflecting effectiveness of schistosomiasis host immunity, were performed using family-based transmission disequilibrium tests for quantitative traits (QTDTs). Alleles A, T and A at the three promoter SNPs rs1800896, rs1800871 and rs1800872 were associated with high tIgE levels in the same direction as in atopy populations (P=0.0008, 0.026 and 0.045), but not with egg counts. IL10 promoter polymorphisms appear to influence non-specific tIgE levels, but not schistosomiasis-specific immunity. The tagging SNP rs3024495 was associated with high S. mansoni egg counts (P=0.005), suggesting a novel locus in IL10 may influence clinically relevant burden of infection.

Rapid reduction in hospitalisations after an intervention to manage severe asthma.

Asthma is the third cause of hospitalisations due to clinical illnesses in Brazil. The Programme for Control of Asthma in Bahia (ProAR) leads an initiative in Salvador City (Brazil) to manage severe asthma for free. The aim of this study was to identify trends in asthma hospitalisation in the entire city and to evaluate the impact of ProAR. Information on asthma hospitalisations from 1998 to 2006 was collected. We analysed trends in Salvador (2.8 million inhabitants) before and after ProAR, taking pneumonia and myocardial infarction into account for local comparison. As an external control we obtained information on asthma from Recife, which is the most comparable Brazilian city. In Salvador, asthma hospital admissions declined by 82.3% (1998-2006). A greater proportion of this reduction (74%) occurred after 2003, in parallel with the implementation of ProAR. The reduction in asthma admissions in Recife was smaller. The rates of hospitalisation in 2006 were 2.25 per 10,000 inhabitants in Salvador and 17.06 in Recife. In Salvador, we found an inverse correlation between the provision of medication for asthma and hospitalisation (-0.801; p<0.0001). A rapid reduction in asthma admissions in the entire city of Salvador was associated with ProAR, a public health intervention targeting severe asthma.

The economic impact of severe asthma to low-income families.

BACKGROUND: To estimate the direct and indirect costs of severe asthma and the economic impact of its management to low-income families in Salvador, Brazil. METHODS: One hundred and ninety-seven patients with severe asthma and referred to a state-funded asthma center providing free treatment were evaluated. At registration, they were asked about family cost-events in the previous year and had a baseline assessment of lung function, symptoms and quality of life. During the subsequent year, they were reassessed prospectively. RESULTS: One hundred-eighty patients concluded a 12-month follow-up. Eighty-four percent were female patients, and the median family income was US$ 2955/year. Forty-seven percent of family members had lost their jobs because of asthma. Total cost of asthma management took 29% of family income. After proper treatment, asthma control scores improved by 50% and quality of life by 74%. The income of the families increased by US$ 711/year, as their members went back to work. The total cost of asthma to the families was reduced by a median US$ 789/family/year. Consequently, an annual surplus of US$ 1500/family became available. CONCLUSIONS: Family costs of severe asthma consumed over one-fourth of the family income of the underprivileged population in a middle-income country. Adequate management brings major economic benefit to individuals and families.

Lack of control of severe asthma is associated with co-existence of moderate-to-severe rhinitis.

BACKGROUND: Retrospective studies provide evidence that rhinitis is associated with more severe asthma. The aim of this study was to evaluate prospectively whether rhinitis is a predictor of increased asthma severity. METHODS: Five hundred and fifty-seven patients with severe asthma were enrolled. During 1 year of follow-up, each patient was evaluated every 3 months with a record of emergency room visits and supply of topical corticosteroids for asthma and rhinitis. In the 1 year of follow-up visit, the patients were checked for rhinitis diagnosis, severity and answered questionnaires for asthma symptoms and quality of life. RESULTS: Eighty-two (15%) patients had no rhinitis, 299 (54%) had mild rhinitis and 176 (31%) moderate/severe rhinitis. In logistic regression models, moderate/severe rhinitis was a predictor for any emergency room visit in the follow-up period [3.83 (2.00-7.35)], for the presence of uncontrolled asthma after 1 year of follow-up [12.68 (1.73-92.85)], for <10% improvement of the airway obstruction [2.94 (1.48-5.85)] and <50% reduction in the number of emergency room visits [2.90 (1.02-8.26)] in the year of follow-up. It was also associated with a smaller chance of more than 90% reduction in the number of emergency room visits in the year of follow-up [0.27 (0.12-0.60)]. In a multivariate linear regression model, severity of rhinitis was positively correlated with a score of asthma severity and inversely correlated to an index of quality of life. CONCLUSIONS: In a population with severe asthma, moderate/severe rhinitis is a strong predictor for greater severity of asthma.

Geohelminth infections: a review of the role of IgE and assessment of potential risks of anti-IgE treatment.

Geohelminth infections are major parasitic infections with a worldwide distribution. Immunoglobulin E (IgE) is considered to play a central role in protective immunity against these parasites although the evidence from experimental animal models infected with helminth parasites and treated with anti-IgE antibodies and from observational studies in human populations of the immunologic correlates of protective immunity against helminths do not support a critical role for IgE in mediating protection against helminths. Anti-IgE treatment of human allergic disorders using a humanized monoclonal IgE antibody (omalizumab, Xolair) has been approved for clinical use in the USA and Europe and there is concern that this treatment may be associated with increased morbidity in populations exposed to helminth infections. A recently published randomized controlled trial investigating the risk of geohelminth infections in allergic patients receiving omalizumab in Brazil has provided some evidence that omalizumab may not be associated with increased morbidity attributable to these parasites. This review examines the evidence for a role of IgE in protective immunity against helminth parasites, discusses the findings of the randomized controlled trial, assesses the potential risks and provides recommendations for anti-IgE treatment in groups of allergic patients with different exposure risks for helminth infections.