Risk factors for severe disease in pediatric respiratory syncytial virus infections.

OBJECTIVES: To assess factors associated with the risk of severe disease in children aged 5 years or younger with laboratory-confirmed respiratory syncytial virus (RSV) infection. STUDY DESIGN: We conducted a nationwide retrospective cohort study in Mexico. METHODS: Eligible participants included children aged 5 years or younger with laboratory-confirmed RSV infection January 1, 2023, and May 15, 2024. We collected relevant clinical and epidemiological data. Risk ratios (RR) and 95% confidence intervals (CI) were employed to identify factors associated with the risk of severe disease, characterized by clinical and radiographic evidence of bronchiolitis or pneumonia requiring hospital admission. RESULTS: Data from 2022 children were analyzed and the overall risk of severe disease was 21.0% (n = 424/2022). In multiple generalized linear regression analysis, a personal history of immunosuppression (due to any cause) showed a protective effect (RR = 0.14, 95% CI 0.05-0.42, P = 0.001) against severe RSV disease, while an increased risk was documented for each additional day elapsed between the date of symptom onset and the date of seeking healthcare RR = 1.06, 95% CI 1.02-1.10, P = 0.004). CONCLUSION: These findings provide insights into risk stratification and suggest specific directions for future research. This information informs the development of targeted intervention strategies to mitigate the impact of RSV infections in this vulnerable population.

An objective tool to measure the effect of botulinum toxin in blepharospasm and hemifacial spasm.

BACKGROUND AND PURPOSE: It is challenging to assess patients with blepharospasm (BSP) and hemifacial spasm (HFS) as these patients exhibit a wide range of amplitudes of eyelid movements. In order to quantify these movements, a mathematical algorithm, i.e. Fast Fourier Transform, can be employed to convert the signal from the time domain to the frequency domain. The result of this quantification represents the energy generated during the eyelid movements. In order to objectively assess the therapeutic effects of botulinum toxin (BoNT) in these patients, we evaluated the energy generated by the upper eyelid during spontaneous eyelid movements before and after treatment. METHODS: A total of 39 patients with BSP and HFS were evaluated before and 30 days after receiving onabotulinum toxin A injections. A high-speed camera and micro light-emitting diodes were used to register the spontaneous eyelid movements. The result of the quantification obtained using Fast Fourier Transform permitted assessment of the activity associated with the eyelid movements. RESULTS: We studied 78 eyelids. The total energy generated during spontaneous eyelid movements was significantly reduced after treatment in the patients with BSP (P = 0.0018) and on the affected side in the patients with HFS (P = 0.0058). CONCLUSIONS: The assessment of the energy generated by the upper eyelid during spontaneous eyelid movements enabled us to measure the therapeutic effects of BoNT in patients with these conditions. The use of this system could enable customized and fine adjustments to BoNT doses based on each patient's needs.

Thermospheric Nitric Oxide Response to Shock-led Storms.

We present a multi-year superposed epoch study of the Sounding of the Atmosphere using Broadband Emission Radiometry nitric oxide (NO) emission data. NO is a trace constituent in the thermosphere that acts as cooling agent via infrared (IR) emissions. The NO cooling competes with storm time thermospheric heating resulting in a thermostat effect. Our study of nearly 200 events reveals that shock-led interplanetary coronal mass ejections (ICMEs) are prone to early and excessive thermospheric NO production and IR emissions. Excess NO emissions can arrest thermospheric expansion by cooling the thermosphere during intense storms. The strongest events curtail the interval of neutral density increase and produce a phenomenon known as thermospheric 'overcooling'. We use Defense Meteorological Satellite Program particle precipitation data to show that interplanetary shocks and their ICME drivers can more than double the fluxes of precipitating particles that are known to trigger the production of thermospheric NO. Coincident increases in Joule heating likely amplify the effect. In turn, NO emissions more than double. We discuss the roles and features of shock/sheath structures that allow the thermosphere to temper the effects of extreme storm time energy input and explore the implication these structures may have on mesospheric NO. Shock-driven thermospheric NO IR cooling likely plays an important role in satellite drag forecasting challenges during extreme events.

Subclinical lower airways correlates of chronic allergic and non-allergic rhinitis.

The upper and lower airways behave as a physiological and pathophysiological unit. Subclinical lower airways abnormalities have been described in patients with rhinitis without asthma. These are expressed as bronchial hyperreactivity, abnormalities in lung function and bronchial inflammation, likely as a result of the same phenomenon with systemic inflammatory impact that reaches both the nose and the lungs, which for unknown reasons does not always have a full clinical expression. Patients with rhinitis are at increased risk of developing asthma; therefore, most authors suggest a careful clinical evaluation and monitoring of these patients, especially if symptoms related to inflammation in the lower airways are observed. Although current treatments, such as H1-antihistamines, intranasal steroids and allergen immunotherapy, are quite effective for the management of rhinitis, it is difficult to prove their capacity to prevent asthma among subjects with rhinitis. Evidence showing that the treatment of rhinitis has a favourable impact on indicators of bronchial hyperreactivity and inflammation among subjects that have no symptoms of asthma is more frequently described. In this review, we address the frequency and characteristics of lower airway abnormalities in subjects with rhinitis, both in paediatric and adult populations, their likely predictive value for the development of asthma and the possibilities for therapeutic intervention that could modify the risk of subjects with rhinitis towards presenting asthma.

The school as a health promoter for children with asthma: The purpose of an education programme.

BACKGROUND: Not only is asthma one of the leading causes of hospitalisation in children under 15 years and one of the main reasons for primary care outpatient visits, it also accounts for 13 million lost days of school annually, which can affect children's learning, integration at school and overall academic achievements. MATERIAL AND METHODS: This review article highlights the important role of the school in helping children and adolescents to control and manage their asthma through integrated and coordinated actions of health professionals, school staff, family, and the community. RESULTS: We recommended key elements for a multidisciplinary team asthma school programme that can be replicated and implemented especially in developing countries where children and adolescents are in a more disadvantaged environment. CONCLUSION: This multidisciplinary asthma school intervention when demonstrated with efficacy can be applied in the context of the real world, where many children and families who need care the most currently do not receive it.

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.

Detection and isolation of Toxoplasma gondii from fresh semen of naturally infected dogs in Southern Brazil.

The aim of this study was to isolate Toxoplasma gondii and determine the viability of the parasite in fresh semen samples of clinically healthy adult dogs naturally infected. Eleven seropositive dogs with T. gondii IgG antibodies from southern Brazil were selected to confirm the presence and viability of T. gondii in fresh semen samples using in vitro isolation in Vero cell culture, polymerase chain reaction (PCR) and sequencing analysis. The presence of viable T. gondii was confirmed by in vitro isolation and PCR in five semen samples. The ITS1 region of the isolated protozoa (TG S4) was amplified and sequenced. The nucleotide sequence obtained was 99% compatible with the T. gondii DNA sequences stored in the GenBank. It has been shown that T. gondii tachyzoites may be isolated in vitro from fresh semen samples of clinically healthy dogs seropositive for T. gondii.

Senescence associated secretory phenotype profile from primary lung mice fibroblasts depends on the senescence induction stimuli.

Cellular senescence is a multifactorial phenomenon of growth arrest and distorted function, which has been recognized as an important feature during tumor suppression mechanisms and a contributor to aging. Senescent cells have an altered secretion pattern called Senescence-Associated Secretory Phenotype (SASP) that comprises a complex mix of factors including cytokines, growth factors, chemokines, and matrix metalloproteinases. SASP has been related with local inflammation that leads to cellular transformation and neurodegenerative diseases. Various pathways for senescence induction have been proposed; the most studied is replicative senescence due to telomere attrition called replicative senescence (RS). However, senescence can be prematurely achieved when cells are exposed to diverse stimuli such as oxidative stress (stress-induced premature senescence, SIPS) or proteasome inhibition (proteasome inhibition-induced premature senescence, PIIPS). SASP has been characterized in RS and SIPS but not in PIIPS. Hence, our aim was to determine SASP components in primary lung fibroblasts obtained from CD-1 mice induced to senescence by PIIPS and compare them to RS and SIPS. Our results showed important variations in the 62 cytokines analyzed, while SIPS and RS showed an increase in the secretion of most cytokines, and in PIIPS only 13 were incremented. Variations in glutathione-redox balance were also observed in SIPS and RS, and not in PIIPS. All senescence types SASP displayed a pro-inflammatory profile and increased proliferation in L929 mice fibroblasts exposed to SASP. However, the behavior observed was not exactly the same, suggesting that the senescence induction pathway might encompass dissimilar responses in adjacent cells and promote different outcomes.

Dangerous waters: outbreak of eye lesions caused by fresh water sponge spicules.

PURPOSE: To describe an extremely uncommon outbreak of eye lesions in a specific area of the Brazilian Amazonia. METHODS: Prospective noncomparative case series. Fifty-nine patients who developed eye lesions after swimming in the Araguaia river of Tocantins state in Brazil were examined. A team of ophthalmologists equipped with a slit-lamp, gonioscopic lenses, and indirect ophthalmoscopy performed full eye examination. Analysis of the flora and fauna of the river water was undertaken by a group of experts. RESULTS AND CONCLUSIONS: Eighty-three eyes were affected. The most common lesions were corneal opacities seen in 34 eyes and conjunctival nodules diagnosed in 12 eyes. Severe visual acuity loss was detected in seven children with unilateral anterior chamber lesions. Spicules of the sponge species Drulia uruguayensis and Drulia ctenosclera were found inside three blind eyes that have been enucleated for diagnostic purposes. All eye lesions could be attributed to an outbreak of foreign bodies from fresh water sponges. Organic enrichment of the water resulting from the absence of sanitation probably was the key factor, which initiated a cycle of ecological imbalance that provoked human disease.

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.

Clinical and immunological features of patients with atopy and concomitant HTLV-1 infection.

Human T-cell lymphotropic virus type 1 (HTLV-1) induces an exacerbated type 1 immune response characterized by high spontaneous IFN-γ and TNF-α production. Allergic rhinitis and asthma are associated with the type 2 immune response, with elevated secretion of IL-4 and IL-5. The aim of this study was to characterize the immune response in atopic HTLV-1 carriers. The cytokine profile of atopic HTLV-1 carriers (N = 10; all females) was compared with that of non-atopic HTLV-1 carriers (N = 14; 9 females and 5 males). Mean patient age of atopic and non-atopic groups was 45 ± 8 and 38 ± 11 years, respectively. All atopic HTLV-1 carriers had rhinitis with or without asthma and a skin prick test positive for Dermatophagoides pteronyssinus antigen 1 (Derp-1). There was no difference in cytokine levels between the two groups in unstimulated peripheral blood mononuclear cell cultures. In cultures stimulated with Derp-1, IFN-γ levels tended to be higher (P = 0.06) and IL-5 levels were higher (P = 0.02) in atopic HTLV-1 patients than in non-atopic subjects. In contrast, IL-10 was lower (P = 0.004) in atopic than in non-atopic HTLV-1-infected subjects. This study shows that HTLV-1 infection with an exaggerated type 1 immune response does not prevent atopy. In this case, the exacerbated type 1 and type 2 immune responses were due to a lack of IL-10 production, a cytokine that plays an important role in down-modulating type 1 and type 2 immune responses and in preventing the development of chronic inflammatory diseases.

Clinical and immunological features of patients with atopy and concomitant HTLV-1 infection

Human T-cell lymphotropic virus type 1 (HTLV-1) induces an exacerbated type 1 immune response characterized by high spontaneous IFN-γ and TNF-α production. Allergic rhinitis and asthma are associated with the type 2 immune response, with elevated secretion of IL-4 and IL-5. The aim of this study was to characterize the immune response in atopic HTLV-1 carriers. The cytokine profile of atopic HTLV-1 carriers (N = 10; all females) was compared with that of non-atopic HTLV-1 carriers (N = 14; 9 females and 5 males). Mean patient age of atopic and non-atopic groups was 45 ± 8 and 38 ± 11 years, respectively. All atopic HTLV-1 carriers had rhinitis with or without asthma and a skin prick test positive for Dermatophagoides pteronyssinus antigen 1 (Derp-1). There was no difference in cytokine levels between the two groups in unstimulated peripheral blood mononuclear cell cultures. In cultures stimulated with Derp-1, IFN-γ levels tended to be higher (P = 0.06) and IL-5 levels were higher (P = 0.02) in atopic HTLV-1 patients than in non-atopic subjects. In contrast, IL-10 was lower (P = 0.004) in atopic than in non-atopic HTLV-1-infected subjects. This study shows that HTLV-1 infection with an exaggerated type 1 immune response does not prevent atopy. In this case, the exacerbated type 1 and type 2 immune responses were due to a lack of IL-10 production, a cytokine that plays an important role in down-modulating type 1 and type 2 immune responses and in preventing the development of chronic inflammatory diseases.

Reduction of asthma burden is possible through National Asthma Plans.

Despite increase in understanding of asthma patomechanisms the practical actions to lessen asthma burden in the communities are far behind of scientific knowledge. There are still reports of uderdiagnosis and poor treatment leading to repeated severe exacerbations, often demanding emergency care and hospitalisation, which cause most of the economic burden both for families and society. From the public health perspective, the key issue is to implement the best standards of care in every-day practice. The problems are different in high income compared to low- and middle-income countries, and the solutions have to be tailored to each country needs and resources. We present here examples from Finland, Poland and Brazil, to show that asthma burden can be reduced using varied strategies in quite different societal, economical and health care environments. The experience from those interventions confirms that regardless of the health care system and its coverage, a major change for the better can be achieved by local efforts, systematic planning and networking to implement the best asthma practice.

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.

Graves' orbitopathy: frequency of ocular hypertension and glaucoma.

PURPOSE: To determine the relationship between ocular hypertension and glaucoma in patients with Graves' orbitopathy. METHODS: A total of 107 patients with a diagnosis of Graves' orbitopathy, followed at the Oculoplasty sector of the University Hospital, Medical School of Ribeirão Preto, were evaluated by applanation tonometry, computed visual campimetry (Humphrey 30-2, Full Threshold) and analysis and photographic documentation of the optic nerve. The patients considered to have the suspicion of glaucoma were re-evaluated 1 year later for diagnostic confirmation or exclusion. RESULTS: A 3.74% prevalence of ocular hypertension (four patients) and a 2.8% prevalence of glaucoma (three patients) was observed. When considering only patients older than 40 years, the prevalence of ocular hypertension was 5.4% (four patients) and the prevalence of glaucoma was 4.76% (three patients). CONCLUSION: The present study did not reveal a statistically significant difference in the prevalence of ocular hypertension or glaucoma between patients with Graves' orbitopathy and the general population.

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.