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1.
Am J Hum Genet ; 110(5): 880-894, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37105174

RESUMO

Using contemporary people as proxies for ancient communities is a contentious but necessary practice in anthropology. In southern Africa, the distinction between the Cape KhoeSan and eastern KhoeSan remains unclear, as ethnicity labels have been changed through time and most communities were decimated if not extirpated. The eastern KhoeSan may have had genetic distinctions from neighboring communities who speak Bantu languages and KhoeSan further away; alternatively, the identity may not have been tied to any notion of biology, instead denoting communities with a nomadic "lifeway" distinct from African agro-pastoralism. The Baphuthi of the 1800s in the Maloti-Drakensberg, southern Africa had a substantial KhoeSan constituency and a lifeway of nomadism, cattle raiding, and horticulture. Baphuthi heritage could provide insights into the history of the eastern KhoeSan. We examine genetic affinities of 23 Baphuthi to discern whether the narrative of KhoeSan descent reflects distinct genetic ancestry. Genome-wide SNP data (Illumina GSA) were merged with 52 global populations, for 160,000 SNPs. Genetic analyses show no support for a unique eastern KhoeSan ancestry distinct from other KhoeSan or southern Bantu speakers. The Baphuthi have strong affinities with early-arriving southern Bantu-speaking (Nguni) communities, as the later-arriving non-Nguni show strong evidence of recent African admixture possibly related to late-Iron Age migrations. The references to communities as "San" and "Bushman" in historic literature has often been misconstrued as notions of ethnic/biological distinctions. The terms may have reflected ambiguous references to non-sedentary polities instead, as seems to be the case for the eastern "Bushman" heritage of the Baphuthi.


Assuntos
Variação Genética , Genética Populacional , Humanos , África Austral , População Negra/genética , Etnicidade/genética
3.
Respirology ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847185

RESUMO

BACKGROUND AND OBJECTIVE: Several randomized controlled trials (RCTs) have shown that benralizumab is characterized by a good profile of efficacy and safety, thereby being potentially able to elicit clinical remission on-treatment of severe eosinophilic asthma (SEA). The main goal of this multicentre observational study was to verify the effectiveness of benralizumab in inducing a sustained remission on-treatment of SEA in patients with or without comorbid chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Throughout 2 years of treatment with benralizumab, a four-component evaluation of sustained remission of SEA was performed, including the assessment of SEA exacerbations, use of oral corticosteroids (OCSs), symptom control and lung function. RESULTS: The present study recruited 164 patients suffering from SEA. After 24 months of add-on biological therapy with benralizumab, 69 (42.1%) achieved the important target of sustained remission on-treatment (exacerbation rate = 0, OCS dose = 0, pre-bronchodilator FEV1 ≥80% pred., ACT score ≥ 20). During the same period, a persistent improvement of CRSwNP (SNOT-22 < 30, NP recurrence = 0) was observed in 33 (40.2%) out of 82 subjects with concomitant NP. The latter comorbidity and post-bronchodilator reversibility of airflow limitation were two independent predictors of sustained remission on-treatment (OR = 2.32, p < 0.05 and OR = 5.59, p < 0.01, respectively). CONCLUSION: Taken together, the results of this real-life clinical investigation indicate that benralizumab can induce a sustained remission on-treatment of SEA, especially in those patients with comorbid CRSwNP and reversible airflow limitation.

4.
Respir Res ; 24(1): 135, 2023 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-37210543

RESUMO

BACKGROUND: The efficacy of benralizumab has been broadly demonstrated in severe eosinophilic asthma (SEA), but only few real-life studies evaluated its long-term effects. Here we present novel data from the ANANKE study in which a large cohort of SEA patients was treated for up to 96 weeks. METHODS: ANANKE (NCT04272463) is an observational retrospective Italian study investigating the key characteristics of SEA patients (collected during the 12 months prior to benralizumab initiation) and the clinical outcomes during benralizumab treatment (annual exacerbation rate [AER], lung function, asthma control, OCS use, healthcare resource utilization). A post hoc analysis was also conducted in groups of patients based on history of previous biologic therapy (bio-experienced versus naïve patients). Analyses were descriptive only. RESULTS: Before benralizumab initiation, evaluable SEA patients (N = 162, 61.1% females, mean age 56.0 ± 12.7) showed a median blood eosinophil count (BEC) of 600 cells/mm3 (IQR: 430-890). Patients experienced frequent exacerbations (annualized exacerbation rate [AER]: 4.10, severe AER: 0.98), with impaired lung function and poor asthma control (median ACT score: 14) despite 25.3% reported oral corticosteroid (OCS) use. Nasal polyposis was present in 53.1% patients; 47.5% patients were atopic. After 96 weeks since the start of benralizumab, nearly 90% patients were still on treatment; benralizumab dramatically decreased exacerbations (AER: - 94.9%; severe AER: - 96.9%), improved respiratory parameters (median increase in pre-bronchodilator forced expiratory volume [pre-BD FEV1]: + 400 mL) and asthma control (median ACT score: 23) while eliminating OCS in 60% patients. Importantly, benralizumab effects were either maintained or progressively improved over time, accompanied by a nearly complete depletion of BEC. Benralizumab reduced AER both in naïve (any AER: - 95.9%; severe AER: - 97.5%) and bio-experienced patients (any AER: - 92.4%; severe AER: - 94.0%). CONCLUSIONS: Profound and sustained improvements in all asthma outcomes were observed with benralizumab. The correct identification of patients' eosinophilic-driven asthma phenotype was essential to ensure the achievement of such remarkable results. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04272463.


Assuntos
Antiasmáticos , Asma , Eosinofilia Pulmonar , Feminino , Masculino , Humanos , Antiasmáticos/efeitos adversos , Estudos Retrospectivos , Progressão da Doença , Método Duplo-Cego , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/induzido quimicamente , Eosinofilia Pulmonar/diagnóstico , Eosinofilia Pulmonar/tratamento farmacológico , Eosinófilos , Corticosteroides/uso terapêutico
5.
Curr Opin Pediatr ; 35(3): 356-361, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36917187

RESUMO

PURPOSE OF REVIEW: Respiratory allergy correlates strictly with air pollution and climate change. Due to climate change, the atmospheric content of trigger factors such as pollens and moulds increase and induce rhinitis and asthma in sensitized patients with IgE-mediated allergic reactions.Pollen allergy is frequently used to evaluate the relationship between air pollution and allergic respiratory diseases. Pollen allergens trigger the release of immunomodulatory and pro-inflammatory mediators and accelerate the onset of sensitization to respiratory allergens in predisposed children and adults. Lightning storms during pollen seasons can exacerbate respiratory allergy and asthma not only in adults but also in children with pollinosis. In this study, we have focalized the trigger (chemical and biologic) factors of outdoor air pollution. RECENT FINDINGS: Environmental pollution and climate change have harmful effects on human health, particularly on respiratory system, with frequent impact on social systems.Climate change is characterized by physic meteorological events inducing increase of production and emission of anthropogenic carbon dioxide (CO 2 ) into the atmosphere. Allergenic plants produce more pollen as a response to high atmospheric levels of CO 2 . Climate change also affects extreme atmospheric events such as heat waves, droughts, thunderstorms, floods, cyclones and hurricanes. These climate events, in particular thunderstorms during pollen seasons, can increase the intensity of asthma attacks in pollinosis patients. SUMMARY: Climate change has important effects on the start and pathogenetic aspects of hypersensitivity of pollen allergy. Climate change causes an increase in the production of pollen and a change in the aspects increasing their allergenic properties. Through the effects of climate change, plant growth can be altered so that the new pollen produced are modified affecting more the human health. The need for public education and adoption of governmental measures to prevent environmental pollution and climate change are urgent. Efforts to reduce greenhouse gases, chemical and biologic contributors to air pollution are of critical importance. Extreme weather phenomena such as thunderstorms can trigger exacerbations of asthma attacks and need to be prevented with a correct information and therapy.


Assuntos
Poluição do Ar , Asma , Produtos Biológicos , Hipersensibilidade , Rinite Alérgica Sazonal , Criança , Humanos , Rinite Alérgica Sazonal/epidemiologia , Rinite Alérgica Sazonal/etiologia , Mudança Climática , Poluição do Ar/efeitos adversos , Asma/etiologia , Asma/complicações , Alérgenos/efeitos adversos
6.
Curr Allergy Asthma Rep ; 23(5): 237-248, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36995525

RESUMO

PURPOSE OF REVIEW: The present review aims to systematically assess published data to elucidate benralizumab efficacy on nasal outcomes in comorbid patients. RECENT FINDINGS: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease of the nasal cavity often associated with severe asthma (SA), contributing to a global disease burden in asthmatics. The two pathologies share common underlying mechanisms (e.g., type-2 inflammation), which sustain symptoms and poor comorbid patient quality of life. Therefore, it is of primary importance to identify the correct therapeutic option in order to achieve the optimal management of patients affected by both pathologies. Benralizumab is a humanized monoclonal antibody directed at the α subunit of the interleukin-5 receptor (IL-5Rα) approved for the treatment of severe eosinophilic asthma. Increasing body of literature provides data on its efficacy also on CRSwNP in the comorbid SA patient. Based on the data described in this review, when benralizumab is administered to comorbid patients, it does not only control severe asthma but also improves CRSwNP clinical outcomes, although we need further studies to add stronger evidence and to improve the correct pheno-endotyping of the comorbid patient.


Assuntos
Asma , Pólipos Nasais , Sinusite , Humanos , Pólipos Nasais/complicações , Pólipos Nasais/tratamento farmacológico , Qualidade de Vida , Asma/complicações , Asma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Doença Crônica , Sinusite/complicações , Sinusite/tratamento farmacológico , Sinusite/epidemiologia
7.
Int J Mol Sci ; 24(3)2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36768778

RESUMO

Add-on biological therapy has proven to be effective in many patients with severe eosinophilic asthma. In this observational multicenter retrospective study, we report the results obtained with mepolizumab and benralizumab in severe asthmatics treated for 12 months in a real-life setting. In these patients, peripheral eosinophil levels, pulmonary function trends, exacerbation rates, systemic corticosteroid use, and symptom control were evaluated during the observation period, to understand which patients met all the criteria in order to be considered in disease remission. The percentage of remittent patients was 30.12% in the mepolizumab-treated subgroup, while in the benralizumab-treated subgroup, patients in complete disease remission were 40%, after 12 months. The results of this study confirm the efficacy of anti-IL-5 biologic drugs in the treatment of severe eosinophilic asthma in a real-life setting.


Assuntos
Antiasmáticos , Asma , Produtos Biológicos , Eosinofilia Pulmonar , Humanos , Antiasmáticos/farmacologia , Antiasmáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Interleucina-5 , Estudos Retrospectivos , Receptores de Interleucina-5/metabolismo
8.
Clin Exp Allergy ; 52(2): 312-323, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34608696

RESUMO

BACKGROUND: Benralizumab is effective in severe eosinophilic asthma (SEA), but suboptimal responses are observed in some patients. Although several factors have been associated with benralizumab response, no cluster analysis has yet been undertaken to identify different responsiveness sub-phenotypes. OBJECTIVE: To identify SEA sub-phenotypes with differential responsiveness to benralizumab. METHODS: One hundred and five patients diagnosed with SEA who had completed 6 months of benralizumab treatment were included in a hierarchical cluster analysis based on a set of clinical variables that can be easily collected in routine practice (age, age at disease onset, disease length, allergen sensitization status, blood eosinophil count, IgE levels, FEV1 % predicted, nasal polyposis, bronchiectasis). RESULTS: Four clusters were identified: Clusters 2 and 3 included patients with high levels of both IgE and eosinophils (type-2 biomarkers high), whereas Clusters 1 and 4 included patients with only one type-2 biomarker at a high level: IgE in Cluster 1 and eosinophils in Cluster 4. Clusters 2 and 3 (both type-2 biomarkers high) showed the highest response rate to benralizumab in terms of elimination of exacerbations (79% and 80% respectively) compared to Clusters 1 and 4 (52% and 60% respectively). When super-response (the absence of exacerbation without oral corticosteroid use) was assessed, Cluster 2, including patients with more preserved lung function than the other clusters, but comparable exacerbation rate, oral corticosteroid use and symptom severity, was the most responsive cluster (87.5% of patients). CONCLUSIONS: Our cluster analysis identified benralizumab differential response sub-phenotypes in SEA, with the potential of improving disease treatment and precision management.


Assuntos
Antiasmáticos , Asma , Antiasmáticos/efeitos adversos , Anticorpos Monoclonais Humanizados , Asma/diagnóstico , Asma/tratamento farmacológico , Análise por Conglomerados , Progressão da Doença , Eosinófilos , Humanos , Fenótipo
9.
Respir Res ; 23(1): 36, 2022 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-35183167

RESUMO

BACKGROUND: Data from phase 3 trials have demonstrated the efficacy and safety of benralizumab in patients with severe eosinophilic asthma (SEA). We conducted a real-world study examining the baseline characteristics of a large SEA population treated with benralizumab in clinical practice and assessed therapy effectiveness. METHODS: ANANKE is an Italian multi-center, retrospective cohort study including consecutive SEA patients who had started benralizumab therapy ≥ 3 months before enrolment (between December 2019 and July 2020), in a real-world setting. Data collection covered (1) key patient features at baseline, including blood eosinophil count (BEC), number and severity of exacerbations and oral corticosteroid (OCS) use; (2) clinical outcomes during benralizumab therapy. We also conducted two post-hoc analyses in patients grouped by body mass index and allergic status. Analyses were descriptive only. RESULTS: Of 218 patients with SEA enrolled in 21 Centers, 205 were evaluable (mean age, 55.8 ± 13.3 years, 61.5% females). At treatment start, the median BEC was 580 cells/mm3 (interquartile range [IQR]: 400-850); all patients were on high-dose inhaled controller therapy and 25.9% were on chronic OCS (median dose: 10 mg/die prednisone-equivalent [IQR: 5-25]); 92.9% experienced ≥ 1 exacerbation within the past 12 months (annualized exacerbation rate [AER] 4.03) and 40.3% reported ≥ 1 severe exacerbation (AER 1.10). During treatment (median duration: 9.8 months [IQR 6.1-13.9]; ≥ 12 months for 34.2% of patients), complete eosinophil depletion was observed; exacerbation-free patients increased to 81% and only 24.3% reported ≥ 1 severe event. AER decreased markedly to 0.27 for exacerbations of any severity (- 93.3%) and to 0.06 for severe exacerbations (- 94.5%). OCS therapy was interrupted in 43.2% of cases and the dose reduced by 56% (median: 4.4 mg/die prednisone-equivalent [IQR: 0.0-10.0]). Lung function and asthma control also improved. The effectiveness of benralizumab was independent of allergic status and body mass index. CONCLUSIONS: We described the set of characteristics of a large cohort of patients with uncontrolled SEA receiving benralizumab in clinical practice, with a dramatic reduction in exacerbations and significant sparing of OCS. These findings support benralizumab as a key phenotype-specific therapeutic strategy that could help physicians in decision-making when prescribing biologics in patients with SEA. Trial registration ClinicalTrials.gov Identifier: NCT04272463.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Eosinófilos/patologia , Antiasmáticos/uso terapêutico , Asma/diagnóstico , Ensaios Clínicos Fase III como Assunto , Progressão da Doença , Feminino , Seguimentos , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Resultado do Tratamento
10.
Proc Natl Acad Sci U S A ; 116(31): 15625-15634, 2019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-31308239

RESUMO

Chronic obstructive pulmonary disease (COPD) is an inflammatory condition associated with abnormal immune responses, leading to airflow obstruction. Lungs of COPD subjects show accumulation of proinflammatory T helper (Th) 1 and Th17 cells resembling that of autoreactive immune responses. As regulatory T (Treg) cells play a central role in the control of autoimmune responses and their generation and function are controlled by the adipocytokine leptin, we herein investigated the association among systemic leptin overproduction, reduced engagement of glycolysis in T cells, and reduced peripheral frequency of Treg cells in different COPD stages. These phenomena were also associated with an impaired capacity to generate inducible Treg (iTreg) cells from conventional T (Tconv) cells. At the molecular level, we found that leptin inhibited the expression of forkhead-boxP3 (FoxP3) and its splicing variants containing the exon 2 (FoxP3-E2) that correlated inversely with inflammation and weakened lung function during COPD progression. Our data reveal that the immunometabolic pathomechanism leading to COPD progression is characterized by leptin overproduction, a decline in the expression of FoxP3 splicing forms, and an impairment in Treg cell generation and function. These results have potential implications for better understanding the autoimmune-like nature of COPD and the pathogenic events leading to lung damage.


Assuntos
Processamento Alternativo/imunologia , Fatores de Transcrição Forkhead , Leptina , Doença Pulmonar Obstrutiva Crônica , Linfócitos T Reguladores , Feminino , Fatores de Transcrição Forkhead/biossíntese , Fatores de Transcrição Forkhead/imunologia , Humanos , Leptina/biossíntese , Leptina/imunologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th1/patologia , Células Th17/imunologia , Células Th17/metabolismo , Células Th17/patologia
11.
Allergy ; 75(9): 2219-2228, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32589303

RESUMO

The impact of climate change on the environment, biosphere, and biodiversity has become more evident in the recent years. Human activities have increased atmospheric concentrations of carbon dioxide (CO2 ) and other greenhouse gases. Change in climate and the correlated global warming affects the quantity, intensity, and frequency of precipitation type as well as the frequency of extreme events such as heat waves, droughts, thunderstorms, floods, and hurricanes. Respiratory health can be particularly affected by climate change, which contributes to the development of allergic respiratory diseases and asthma. Pollen and mold allergens are able to trigger the release of pro-inflammatory and immunomodulatory mediators that accelerate the onset the IgE-mediated sensitization and of allergy. Allergy to pollen and pollen season at its beginning, in duration and intensity are altered by climate change. Studies showed that plants exhibit enhanced photosynthesis and reproductive effects and produce more pollen as a response to high atmospheric levels of carbon dioxide (CO2 ). Mold proliferation is increased by floods and rainy storms are responsible for severe asthma. Pollen and mold allergy is generally used to evaluate the interrelation between air pollution and allergic respiratory diseases, such as rhinitis and asthma. Thunderstorms during pollen seasons can cause exacerbation of respiratory allergy and asthma in patients with hay fever. A similar phenomenon is observed for molds. Measures to reduce greenhouse gas emissions can have positive health benefits.


Assuntos
Asma , Hipersensibilidade , Alérgenos , Asma/epidemiologia , Asma/etiologia , Mudança Climática , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/etiologia , Pólen
12.
Curr Allergy Asthma Rep ; 20(3): 8, 2020 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-32103354

RESUMO

PURPOSE OF REVIEW: It is well known that combination of sensitization and exposure to inhaled environmental allergens is related to both the development and elicitation of symptoms of asthma and that avoidance of allergens would exert beneficial effects in the prevention and control of the disease. Other important factors include the relevance of other allergens, exposure to sensitizing agents also outside patient's home, exposure to irritants (like chemical air pollutants), and the involvement of the patient with a correct education. It is also likely that clinical phase of allergic airway disease and the degree of airways remodeling represent relevant factors for the clinical outcome of allergen avoidance procedure. We reviewed existing evidence on prevention of asthma through allergen avoidance. RECENT FINDINGS: The management of respiratory allergy is a complex strategy (including prevention, drugs, immunological, and educational interventions). In addition, it is difficult in real life to distinguish the efficacy of single interventions. However, a combined strategy is likely to produce clinical results. A combined strategy is likely to produce satisfactory management of asthma. Allergens are an important trigger factor for the development of symptoms of respiratory allergy, and avoidance measures are able to reduce allergen levels. It is likely that clinical phase of allergic airway disease and the degree of airways remodeling represents relevant factors for the clinical outcome of allergen avoidance procedures. Considering the management of respiratory allergy is a complex strategy; it is difficult in real life to distinguish the efficacy of single interventions. However, further studies better quantifying the effects of allergens are needed.


Assuntos
Alérgenos/efeitos adversos , Asma/prevenção & controle , Expossoma , Prevenção Primária/métodos , Poluentes Atmosféricos , Animais , Asma/etiologia , Humanos , Hipersensibilidade/etiologia
13.
Int J Legal Med ; 133(6): 1681-1689, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30982129

RESUMO

In forensic casework, Y-chromosome short tandem repeats (Y-STRs) are essential for differentiating between unrelated males and resolving the male component of admixed biological evidence. While the majority of Y-STRs are adequate for discriminating between different paternal lineages, rapidly mutating Y-STRs are necessary for improving discrimination between males within populations of low Y-chromosome diversity and between paternal relatives. Alternatively, sequencing of Y-STRs may also improve the discrimination between isometric Y-STR alleles by identifying variation in the repeat unit pattern arrangements and by identifying SNPs in the flanking region or within the STR repeat unit itself. In this report, a total of 153 DNA sequences are presented across the Y-STR loci DYS710, DYS518, DYS385, DYS644, DYS612, DYS626, DYS504, DYS481, DYS447 and DYS449. A total of 94 Y-STR sequences provided herein are reported for the first time, of which 37 sequences represent alleles showing size homoplasy, 34 sequences of known alleles for which sequence data has been unavailable and a total of 23 novel allele sequences across loci DYS644, DS447, DYS710 and DYS504. This study further encountered a rare sequence variant in the 5' flanking region of DYS385 and a total of two SNPs in the repeat structure at DYS481 and DYS449.


Assuntos
Cromossomos Humanos Y , Variação Genética , Repetições de Microssatélites , Análise de Sequência de DNA , Região 5'-Flanqueadora , Alelos , Impressões Digitais de DNA , Marcadores Genéticos , Humanos , Masculino , Reação em Cadeia da Polimerase
14.
Curr Allergy Asthma Rep ; 18(4): 24, 2018 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-29574559

RESUMO

PURPOSE OF REVIEW: There are observations in various geographical areas that thunderstorms occurring during pollen seasons can induce severe asthma attacks in pollinosis patients. RECENT FINDINGS: An accredited hypothesis explaining the association between thunderstorms and asthma suggests that storms can concentrate pollen grains at ground level, which may then release allergenic particles of respirable size in the atmosphere after their imbibition of water and rupture by osmotic shock. During the first 20-30 min of a thunderstorm, patients affected by pollen allergy may inhale a high quantity of the allergenic material that is dispersed into the atmosphere as a bioaerosol of allergenic particles, which can induce asthmatic reactions, often severe. Subjects without asthma symptoms, but affected by seasonal rhinitis can also experience an asthma attack. A key message is that all subjects affected by pollen allergy should be alerted to the danger of being outdoors during a thunderstorm in the pollen season, as such events may be an important cause of severe asthma exacerbations. In light of these observations, it is useful to predict thunderstorms and thus minimize thunderstorm-related events. Patients with respiratory allergy induced by pollens and molds need to be informed about a correct therapeutic approach of bronchial asthma by inhalation, including the use of bronchodilators and inhaled corticosteroids. The purpose of this review is to focalize epidemiological, etiopathogenetic, and clinical aspects of thunderstorm-related asthma.


Assuntos
Asma , Processos Climáticos , Alérgenos , Humanos , Pólen , Estações do Ano
15.
J Allergy Clin Immunol ; 139(5): 1536-1547.e5, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27746236

RESUMO

BACKGROUND: Epidemiologic and clinical evidence supports the existence of an obesity-related asthma phenotype. No distinct pathophysiologic elements or specific biomarkers have been identified thus far, but increased oxidative stress has been reported. OBJECTIVE: We aimed at verifying whether metabolomics of exhaled breath condensate from obese asthmatic (OA) patients, lean asthmatic (LA) patients, and obese nonasthmatic (ONA) subjects could recognize specific and statistically validated biomarkers for a separate "asthma-obesity" respiratory metabolic phenotype, here defined as "metabotype." METHODS: Twenty-five OA patients, 30 ONA subjects, and 30 mild-to-moderate LA age-matched patients participated in a cross-sectional study. Nuclear magnetic resonance (NMR) profiles were analyzed by using partial least-squares discriminant analysis, and the results were validated with an independent patient set. RESULTS: From NMR profiles, we obtained strong regression models that distinguished OA patients from ONA subjects (quality parameters: goodness-of-fit parameter [R2] = 0.81 and goodness-of-prediction parameter [Q2] = 0.79), as well as OA patients from LA patients (R2 = 0.91 and Q2 = 0.89). The all-classes comparison (R2 = 0.86 and Q2 = 0.83) indicated that OA patients possess a respiratory metabolic profile fully divergent from those obtained in the other patient groups. We also identified specific biomarkers for between-class separation, which are independent from clinical bias. They are involved in the methane, pyruvate, and glyoxylate and dicarboxylate metabolic pathways. CONCLUSIONS: NMR-based metabolomics indicates that OA patients are characterized by a respiratory metabolic fingerprint fully different from that of patients independently affected by asthma or obesity. Such a phenotypic difference strongly suggests unique pathophysiologic pathways involved in the pathogenesis of asthma in adult obese subjects. Furthermore, the OA metabotype could define a strategy for patient stratification based on unbiased biomarkers, with important diagnostic and therapeutic implications.


Assuntos
Asma/metabolismo , Obesidade/metabolismo , Adulto , Biomarcadores/metabolismo , Testes Respiratórios , Estudos Transversais , Feminino , Humanos , Masculino , Metabolômica , Pessoa de Meia-Idade , Fenótipo , Espectroscopia de Prótons por Ressonância Magnética
16.
Electrophoresis ; 38(5): 617-623, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27859383

RESUMO

CE equipment detects and deconvolutes mixtures containing up to six fluorescently labeled DNA fragments. This deconvolution is done by the collection software that requires a spectral calibration file. The calibration file is used to adjust for the overlap that occurs between the emission spectra of fluorescence dyes. All commercial genotyping and sequencing kits require the installation of a corresponding matrix standard to generate a calibration file. Due to the differences in emission spectrum overlap between fluorescent dyes, the application of existing commercial matrix standards to the electrophoretic separation of DNA labeled with other fluorescent dyes can yield undesirable results. Currently, the number of fluorescent dyes available for oligonucleotide labeling surpasses the availability of commercial matrix standards. Therefore, in this study we developed and evaluated a customized matrix standard using ATTO 633, ATTO 565, ATTO 550, ATTO Rho6G, and 6-FAM dyes for which no commercial matrix standard is available. We highlighted the potential genotyping errors of using an incorrect matrix standard by evaluating the relative performance of our custom dye set using six matrix standards. The specific performance of two genotyping kits (UniQTyper™ Y-10 version 1.0 and PowerPlex® Y23 System) was also evaluated using their specific matrix standards. The procedure we followed for the construction of our custom dye matrix standard can be extended to other fluorescent dyes.


Assuntos
Automação Laboratorial/normas , Eletroforese Capilar/normas , Corantes Fluorescentes/análise , Corantes Fluorescentes/normas , Técnicas de Genotipagem/normas , Automação Laboratorial/métodos , Eletroforese Capilar/métodos , Corantes Fluorescentes/química , Técnicas de Genotipagem/métodos , Projetos de Pesquisa
17.
Curr Opin Pulm Med ; 23(1): 103-108, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27820743

RESUMO

PURPOSE OF REVIEW: Current guidelines recommend a stepwise approach for pharmacological therapy aimed to achieve and maintain asthma control. Despite these recommendations, at least 50% of patients continue to be uncontrolled with risk of asthma exacerbations that can often be serious and are associated with deterioration of quality of life. In recent years, the interest in anticholinergic bronchodilators, which have been primarily used in the treatment of chronic obstructive pulmonary disease, has increased patients with uncontrolled asthma. This review analyzes the mechanisms for the proposed clinical use of anticholinergic bronchodilators as an adjunctive therapy in asthma. RECENT FINDINGS: Based on existing and recent evidence, the use of anticholinergic bronchodilators, particularly long-acting muscarinic antagonists (LAMAs), plays an important role as add-on therapy in patients uncontrolled on existing therapies. In particular, the use of anticholinergics in asthma may have a role in patients intolerant to long-acting ß2 agonist, in patients with certain pharmacogenetic profiles and in those patients with asthma symptoms mostly at night. SUMMARY: Data from clinical trials and from real-life confirm the safety and efficacy of LAMAs, especially tiotropium, in patients who remain uncontrolled despite the use of inhaled corticosteroid therapy.


Assuntos
Asma/tratamento farmacológico , Antagonistas Colinérgicos/uso terapêutico , Quimioterapia Combinada , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Qualidade de Vida
18.
Pulm Pharmacol Ther ; 44: 83-87, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28341462

RESUMO

BACKGROUND: Asthma considerably impairs patients' quality of life and increases healthcare costs. Severity, morbidity, and degree of disease control are the major drivers of its clinical and economic impact. National scientific societies are required to monitor the application of international guidelines and to adopt strategies to improve disease control and better allocate resources. AIM: to provide a detailed picture of the characteristics of asthma patients and modalities of asthma management by specialists in Italy and to develop recommendations for the daily management of asthma in a specialist setting. METHOD: A quantitative research program was implemented. Data were collected using an ad hoc questionnaire developed by a group of specialists selected by the Italian Pneumology Society/Italian Respiratory Society. RESULTS: The records of 557 patients were analyzed. In the next few years, specialists are expected to focus their activity patients with more severe disease and will be responsible for selection of patients for personalized biological therapy; however, only 20% of patients attending Italian specialist surgery can be considered severe. In 84.4% of cases, the visit was a follow-up visit requested in 82.2% of cases by the specialist him/herself. The Asthma Control Test is used only in 65% of patients. When available, a significant association has been observed between the test score and asthma control as judged by the physician, although concordance was only moderate (κ = 0.68). Asthma was considered uncontrolled by the specialist managing the case in 29.1% of patients; nevertheless, treatment was not stepped up in uncontrolled or partly controlled patients (modified in only 37.2% of patients). CONCLUSIONS: The results of this survey support re-evaluation of asthma management by Italian specialists. More resources should be made available for the initial visit and for more severely ill patients. In addition, more extensive use should be made of validated tools, and available drugs should be used more appropriately.


Assuntos
Asma/terapia , Padrões de Prática Médica/estatística & dados numéricos , Qualidade de Vida , Especialização , Adulto , Idoso , Asma/fisiopatologia , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários
19.
BMC Med Imaging ; 17(1): 52, 2017 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-28859628

RESUMO

BACKGROUND: Chest X-ray (CXR) is the primary diagnostic tool for community-acquired pneumonia (CAP). Some authors recently proposed that thoracic ultrasound (TUS) could valuably flank or even reliably substitute CXR in the diagnosis and follow-up of CAP. We investigated the clinical utility of TUS in a large sample of patients with CAP, to challenge the hypothesis that it may be a substitute for CXR. METHODS: Out of 645 consecutive patients with a CXR-confirmed CAP diagnosed in the emergency room of our hospital over a three-years period, 510 were subsequently admitted to our department of Internal Medicine. These patients were evaluated by TUS by a well-trained operator who was blinded of the initial diagnosis. TUS scans were performed both at admission and repeated at day 4-6th and 9-14th during stay. RESULTS: TUS identified 375/510 (73.5%) of CXR-confirmed lesions, mostly located in posterior-basal or mid-thoracic areas of the lungs. Pleural effusion was detected in 26.9% of patients by CXR and in 30.4% by TUS. TUS documented the change in size of the consolidated areas as follows: 6.3 ± 3.4 cm at time 0, 2.5 ± 1.8 at 4-6 d, 0.9 ± 1.4 at 9-14 d. Out of the 12 patients with delayed CAP healing, 7 of them turned out to have lung cancer. CONCLUSIONS: TUS allowed to detect lung consolidations in over 70% of patients with CXR-confirmed CAP, but it gave false negative results in 26.5% of cases. Our longitudinal results confirm the role of TUS in the follow-up of detectable lesions. Thus, TUS should be regarded as a complementary and monitoring tool in pneumonia, instead of a primary imaging modality.


Assuntos
Pneumonia/diagnóstico , Tórax/diagnóstico por imagem , Adulto , Idoso , Infecções Comunitárias Adquiridas/diagnóstico , Reações Falso-Negativas , Feminino , Humanos , Pacientes Internados , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Ultrassonografia
20.
Epidemiol Prev ; 41(3-4): 208-211, 2017.
Artigo em Italiano | MEDLINE | ID: mdl-28929717

RESUMO

An increasing body of evidence shows the occurrence of asthma epidemics, sometimes also severe, during thunderstorms in the pollen season in various geographical zones. The main hypothesis explaining association between thunderstorms and asthma claims that thunderstorms can concentrate pollen grains at ground level; these grains may then release allergenic particles of respirable size in the atmosphere after their rupture by osmotic shock. During the first 20-30 minutes of a thunderstorm, patients suffering from pollen allergy may inhale a high concentration of the allergenic material dispersed into the atmosphere, which can, in turn, induce asthmatic reactions, often severe. Subjects without asthma symptoms but affected by seasonal rhinitis can also experience an asthma attack. All subjects affected by pollen allergy should be alerted to the danger of being outdoors during a thunderstorm in the pollen season, as such events may be an important cause of severe bronchial obstruction. Considering this background, it is useful to predict thunderstorms during pollen season and, thus, to prevent thunderstorm-related clinical event. However, it is also important to focus on therapy, and it is not sufficient that subjects at risk of asthma follow a correct therapy with bronchodilators, but they also need to inhale corticosteroids, using both in case of emergency.


Assuntos
Asma/epidemiologia , Surtos de Doenças , Pólen , Estações do Ano , Asma/etiologia , Humanos , Pólen/efeitos adversos , Chuva
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