Clinical asthma phenotypes in the real world: opportunities and challenges

Key PointsAsthma is a heterogeneous syndrome ranging from mild disease with barely noticeable symptoms to very severe disease with constant symptoms that may greatly hinder patients’ quality of life.The aim of asthma treatment is control of asthma and the prevention of risk of exacerbations and fixed airflow limitation.Asthma management must be individualised; tailored not only to the severity of the disease but importantly, to the phenotypic characteristics of the patient and modified according to response to treatment.Educational AimsTo inform readers about the current understanding on the treatment of asthma.To highlight the usefulness of phenotypes in treating asthmatic patients, especially those with severe disease.To introduce the issues of severe asthma management and future planning.Asthma is a common, chronic and heterogeneous syndrome, affecting people of all ages, all races and both sexes. It may range from mild disease with barely noticeable symptoms, to very severe disease with constant symptoms that greatly hinder the life of the patient. Guidelines issued by various medical societies provide guidance on how to diagnose and manage asthmatic patients. It is now increasingly recognised that asthma management must be individualised, tailored not only to the severity of the disease but to the phenotypic characteristics of each patient. The aim of asthma treatment is control of asthma and the prevention of risk of exacerbations and fixed airflow limitation. Asthma control can be easily assessed clinically through simple screening tools such as the use of validated questionnaires and spirometry. The use of inflammatory biomarkers can be an alternative approach that, however, requires more time and resources. Asthma treatment involves the use of controllers, mainly inhaled corticosteroids and long-acting β2-agonists, and relievers, mainly rapid-acting β2-agonists. Controller medications reduce airway inflammation, lead to better symptom control and reduce the risk of future exacerbations. Reliever (rescue) medications alleviate symptoms and prevent exercise-induced bronchoconstriction. Treatment must be based on a “stepwise approach” in order to achieve good control of symptoms and to minimise future risks of exacerbations. That is, less treatment for mild disease, more treatment for severe, uncontrolled disease. Once good asthma control has been achieved and maintained, treatment should be stepped down. In severe asthmatics, phenotypic characterisation becomes more clinically useful and add-on treatment such as anti-immunoglobulin E monoclonal antibodies may be required. Despite our better understanding of asthma, there are still patients who will not respond to treatment and remain symptomatic. Dissemination of guidelines and national plans allowing early diagnosis of asthma as well as access to specialised primary and secondary care for asthmatic patients, personalised treatment and continuity of care may lead to excellence in care and controlled asthma for the majority of patients. Education of the patient in asthma is also very important, as in every chronic disease, as the patients live with the disease every day while they visit a healthcare professional a few times a year. Future planning for new treatments should focus on the needs of such severe asthma patients.

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Asthmatics Treatment Updation and Compliance in the Asthma Management in Northern Districts of Tamilnadu

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i3.2819 ◽

2020 ◽

Vol 11 (3) ◽

pp. 4990-4997

Author(s):

Mani Dhandayuthapani ◽

Murugesh Shivashankar

Keyword(s):

Asthma Management ◽

P Value ◽

Asthma Treatment ◽

Women Patients ◽

Medical Practitioners ◽

Asthmatic Patients ◽

The Social ◽

Asthma Patients ◽

Social Statistics

The purpose of this study is to evaluate the treatment of asthmatics in Tamilnadu's northern districts and its compliance in socio-economic aspects. A random sampling, and the non comparative study conducted among 500 asthmatic people around the northern districts of Tamilnadu, including Chennai, Kanchipuram, Vellore, and Puducherry. The questionnaire asked the asthmatics about their treatment updation, and compliance in asthma management, in an open-ended and easily understandable manner. The P-value calculated through the social statistics software and p-value of <0.10 was considered statistically significant. A total of 500 patients enrolled in this study. Total Men asthmatic patients enrolled were 272(55.4%), and women patients were 228(45.6). In asthma, there are two types of drugs involved in the treatment.1.Reliever drugs and 2. Controller drugs. Four hundred seventeen patients in treatment, 6% of patients were in reliever treatment, 69% were in the controlled, and 25% in both the drugs treatment, respectively.In addition,patients in ICS+ LABA combination was 390.21% of patients were in Formoterol+ Beclomethasone(FBE) combination, 39% in Formoterol +Budesonide(FBU), 6% in Formoterol+Fluticasone(FF),4% in Formoterol+Momentasone(FM) and 30% in Salmeterol+Fluticasone(SF). Money spent on their treatment.24% patients spent less than Rs.150 for their asthma treatment for a month, 29% spent Rs.150-300 and more than Rs 300 spent by 47% of the patients. In Asthma Management, Medical practitioners had prescribed ICS +LABA combination for their asthma patients; as a result, patients felt an improved quality of life.

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Two distinct mechanisms underlie dosage sensitivity in Pumilio1-associated diseases

10.1101/2021.03.11.435015 ◽

2021 ◽

Author(s):

Salvatore Botta ◽

Nicola de Prisco ◽

Alexei Chemiakine ◽

Maximilian Cabaj ◽

Vicky L. Brandt ◽

...

Keyword(s):

Brain Region ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Late Onset ◽

Severe Disease ◽

List Type ◽

Mild Disease ◽

The Difference ◽

Modest Reduction

SUMMARYThe RNA-binding protein (RBP) Pumilio1 (PUM1) is associated with two distinct diseases: a late-onset ataxia and a neurodevelopmental syndrome. The ataxia patients retain 75% of normal PUM1 levels, the syndromic patients ∼50%, but this seems inadequate to explain the difference in phenotypes. We hypothesized that mild disease results from dysregulation of PUM1 targets, whereas severe disease involves disruption of PUM1 complexes and deregulation of shared targets. We therefore developed a PUM1 interactome for the murine brain and found that PUM1 shares targets with several RBP interactors (PUM2, FMRP, AGO2, and RBFOX3). PUM1 haploinsufficiency destabilizes these RBPs to varying degrees by brain region and sex, and alters expression of their shared targets, but the milder disease-causing mutation affects only PUM1-specific targets. These data indicate that dosage-sensitive proteins can produce different phenotypes by different mechanisms, and that there may be more intimate cooperation among RBPs than expected.HIGHLIGHTS•RNA-binding proteins can cause disease via their targets or interactors•Interactions among RNA-binding proteins can differ by brain region and sex•A modest reduction in PUM1 levels affects PUM1-specific targets•Greater reductions in PUM1 levels disrupt interactors and shared targets

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Evidence for lifestyle interventions in asthma

Breathe ◽

10.1183/20734735.0019-2019 ◽

2019 ◽

Vol 15 (2) ◽

pp. e50-e61 ◽

Cited By ~ 5

Author(s):

Isobel Stoodley ◽

Lily Williams ◽

Cherry Thompson ◽

Hayley Scott ◽

Lisa Wood

Keyword(s):

Quality Of Life ◽

Physical Activity ◽

Weight Loss ◽

Asthma Control ◽

Asthma Management ◽

Massage Therapy ◽

List Type ◽

Lifestyle Interventions ◽

Asthmatic Patients

Asthma is a chronic inflammatory airways disease, estimated to affect 300 million people worldwide. Asthma management plans focus on optimisation of asthma pharmacotherapy. Lifestyle interventions also hold great promise for asthma sufferers as they are accessible, low cost and have minimal side-effects, thus making adherence more likely. This review explores lifestyle interventions that have been tested in asthma, including improving nutrition, increasing physical activity and introduction of relaxation therapies such as yoga and massage therapy. Available evidence suggests a protective effect of increasing fruit, vegetable and wholegrain intake and increasing physical activity levels in asthma. Weight loss is recommended for obese asthmatic patients, as just 5–10% weight loss has been found to improve quality of life and asthma control in most obese asthmatic patients. Other lifestyle interventions such as meditation, yoga and massage therapy show promise, with positive effects on asthma seen in some studies. However, the study protocols are highly variable and the results are inconsistent. Additional research is needed to further develop and refine recommendations regarding lifestyle modifications that can be implemented to improve asthma.Key pointsImproving diet quality, by increasing fruit, vegetable and wholegrain intake and reducing saturated fat intake, should be recommended in asthma, as there is evidence suggesting that this leads to improvements in airway inflammation, asthma control and exacerbation risk.Regular physical activity should be promoted for people with asthma, as it can improve quality of life and lung function, as well as general health.In obese asthmatic patients, weight loss should be recommended, as it leads to numerous health benefits, including improvements in asthma. Even small amounts of weight loss in adults (5–10% body weight) have been shown to improve asthma quality of life and asthma control in the majority of people with asthma.There is some evidence of benefit of meditation, yoga and breathing exercises for adults with asthma, while massage therapy shows promise in children with asthma. However, the evidence is inconsistent and more research is needed to make definitive recommendations.Educational aimsTo summarise current knowledge on lifestyle interventions in asthma.To improve awareness of how lifestyle modification can be used in asthma management.To identify areas for future research on lifestyle interventions in asthma.

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Early and Strong Antibody Responses to SARS-CoV-2 Predict Disease Severity in COVID-19 Patients

10.21203/rs.3.rs-1219833/v1 ◽

2022 ◽

Author(s):

Jānis Plūme ◽

Artis Galvanovskis ◽

Sindija Šmite ◽

Nadezda Romanchikova ◽

Pawel Zayakin ◽

...

Keyword(s):

Cell Activation ◽

Severe Disease ◽

Prognostic Significance ◽

Serum Levels ◽

Epidemiological Studies ◽

Antibody Responses ◽

Mast Cell Activation ◽

N Protein ◽

Mild Disease ◽

Severity Of The Disease

Abstract Background Antibody response to SARS-CoV-2 is a valuable biomarker for the assessment of the spread of the virus in a population and evaluation of the vaccine candidates. Recent data suggest that antibody levels also may have a prognostic significance in COVID-19. Most of the serological studies so far rely on testing antibodies against spike (S) or nucleocapsid (N) protein, however antibodies can be directed against other structural and nonstructural proteins of the virus, whereas their frequency, biological and clinical significance is unknown. Methods A novel antigen array comprising 30 SARS-CoV-2 antigens or their fragments was developed and used to examine IgG, IgA, IgE and IgM responses to SARS-CoV-2 in sera from 103 patients with COVID-19 including 34 patients for whom sequential samples were available, and 20 pre-pandemic healthy controls. Results Antibody responses to various antigens are highly correlated and the frequencies and peak levels of antibodies are higher in patients with severe/moderate disease than in those with mild disease. This finding supports the idea that antibodies against SARS-CoV-2 may exacerbate the severity of the disease via antibody-dependent enhancement. Moreover, early IgG and IgA responses to full length S protein may be used as an additional biomarker for the identification of patients who are at risk of developing severe disease. Importantly, this is the first study reporting that SARS-CoV-2 elicits IgE responses and their serum levels positively correlate with the severity of the disease thus suggesting a link between high levels of antibodies and mast cell activation. Conclusions This is the first study assessing the prevalence and dynamics IgG, IgA, IgE and IgM responses to multiple SARS-CoV-2 antigens simultaneously. Results provide important insights into the pathogenesis of COVID-19 and have implications in planning and interpreting antibody-based epidemiological studies.

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Familial aggregation of COVID-19 severity suggests a genetic component to host infection response

Journal of Clinical Images and Medical Case Reports ◽

10.52768/2766-7820/1077 ◽

2021 ◽

Vol 2 (2) ◽

Author(s):

Alexandre R Vieira ◽

Keyword(s):

Familial Aggregation ◽

Severe Disease ◽

Case Series ◽

Genetic Component ◽

Mild Disease ◽

Individual Host ◽

Disease Pattern ◽

Infection Response ◽

Severity Of The Disease ◽

Host Infection

Familial aggregation of COVID-19 cases suggest transmission occurs by contact but can also be evidence of a genetic component to the disease presentation. The goal of this work was to evaluate the disease pattern in families that many individuals have been affected by the disease. A case series analysis of six families that had many individuals affected by COVID-19 and the pattern of the severity of the disease is reported. Families were from two densely populated cities in Brazil. Participants included family members of six unrelated families, with some individuals that showed signs of COVID-19. The exposure was SARS-CoV-2 in the same household. The main outcomes and measures were disease affection and severity, including mortality. From the six families, two had mild cases only, whereas the other four families showed severe disease and death in the same sibship. The two families that had mild disease could be followed for six months and one showed reinfection after six months. This cases series suggest that disease severity aggregates in families, which suggests a genetic component for individual host response to SARS-CoV-2 infection.

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Bordetella pertussis surveillance in England and Wales: 1995–7

Epidemiology and Infection ◽

10.1017/s0950268899003052 ◽

1999 ◽

Vol 123 (3) ◽

pp. 403-411 ◽

Cited By ~ 61

Author(s):

P. G. VAN BUYNDER ◽

D. OWEN ◽

J. E. VURDIEN ◽

N. J. ANDREWS ◽

R. C. MATTHEWS ◽

...

Keyword(s):

Bordetella Pertussis ◽

Hospital Admissions ◽

Severe Disease ◽

Disease Onset ◽

Booster Vaccination ◽

Late Summer ◽

Background Rate ◽

England And Wales ◽

Mild Disease ◽

Severity Of The Disease

Available data sources on disease due to Bordetella pertussis, including notifications, hospital admissions, deaths, and an enhanced laboratory-based surveillance system commenced in January 1994, were reviewed for the period 1995–7. Pertussis notifications continued their approximately 3-year cycle although at historically reduced levels. A slight seasonal increase in late summer/early autumn existed over and above a relatively constant background rate. Over time, the proportion of pertussis cases in younger, unvaccinated children, and to a lesser extent, adolescents and young adults, is increasing. There is a continuing significant and under- reported mortality associated with pertussis in the very young age group. Disease due to serotype 1,2 is on the increase despite persistent high vaccination levels and this serotype causes more severe disease. The provision of preventative antibiotics prior to disease onset reduced the severity of the disease but its use remains uncommon in England and Wales. While overall levels of pertussis notifications have declined in recent times, vaccination efficacy wanes with increasing age, and pertussis remains a significant cause of mortality and severe morbidity in the very young. This could be reduced by timely booster vaccination and increased recognition of mild disease in older cases followed by early antibiotic therapy for the very young household contacts.

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SAT0541 THE SEVERITY OF FMF MAY BE ASSOCIATED WITH CO-MORBIDITIES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.801 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1227.3-1228

Author(s):

M. E. Tezcan ◽

N. Şen ◽

M. Yilmaz ◽

Ö. Volkan ◽

E. Tükel ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Scoring System ◽

Disease Duration ◽

Severe Disease ◽

Smoking History ◽

Disease Group ◽

Severity Scoring ◽

Mild Disease ◽

Co Morbidity ◽

Mediterranean Fever

Background:Familial Mediterranean fever (FMF) is an auto inflammatory disease with recurrent attacks of serositis. Frequent attacks and disease related sequels may be associated with co-morbidities in FMF patients.Objectives:One of the tools for evaluating the FMF severity is the international severity scoring system for FMF (ISSF)1. This score includes disease related sequels, acute phase measurements, attack features and exertional leg pain. Therefore, more severe disease may be link with subclinical inflammation, amyloidosis and frequent, prolonged and widespread attacks. All these components may augment the frequency of non-disease related co-morbidities.Methods:We enrolled 158 FMF patients who fulfilled modifiedTel-HashomerDiagnosisCriteria2. The patients dichotomized based upon disease severity (mild disease or severe disease). Patients with ISSF scores lower or equal to 2 were accepted to have mild disease. Then, we compared frequency of non-disease related co-morbidities between the groups. These co-morbidities arehypertension, hypothyroidism, hyperthyroidism cardiovascular diseases, coronary artery diseases, cerebrovascular diseases, chronic renal disease (non-FMF related), chronic obstructive pulmonary diseases, and diabetes mellitus. This study was approved by the Local Research Ethics Committee and carried out in compliance with the Helsinki Declaration. All the patients gave written informed consent. P-value lower than 0.05 was considered as statistically significant.Results:Demographic features, disease duration, smoking history and body mass index (BMI) were similar between the groups. Frequency of co-morbidity in severe disease group was statistically higher than mild disease group (p=0.02). Most frequent co-morbidity was hypertension in both groups.Table.Features of mild and severe FMF groupsMild (n=135)Severe (n=23)pGender (M/F)47/8811/120.23Age36.4±11.336.5±14.30.68Smoking (%)38 (28.1)5 (21.7)0.52BMI (kg/m2)24.3±9.224.0±8.90.34Disease duration (year)7.7±11.38.6±14.30.09Amyloidosis (%)2 (1.4)3 (13.0)0.02Exon 10 homozygote (%)35 (25.9)9 (39.1)0.19Colchicine dosage (mg/day)1.2±0.41.4±0.50.02ISSF scores0.7 ±0.73.4±0.5<0.001Co-morbidity (%)25 (18.5)9 (39.1)0.02Conclusion:In our FMF patient cohort, we found that severity of the disease may be associated with higher frequency of co-morbidities. Therefore, clinicians should be aware of the high possibility of co-morbidities in patients with more severe FMF and addressed these co-morbidities timely and properly.References:[1]Demirkaya E, et al. Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF). Ann Rheum Dis 2016;75:1051-6.[2]Berkun Y, et al. Diagnostic criteria of familial Mediterranean fever. Autoimmun Rev 2014;13:388-90.Acknowledgments:NoneDisclosure of Interests:None declared

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A Case Series of SARS-CoV-2 RT-PCR-Positive Hospitalized Infants 60 Days of Age or Younger From 2 New York City Pediatric Emergency Departments

Clinical Pediatrics ◽

10.1177/00099228211006688 ◽

2021 ◽

Vol 60 (4-5) ◽

pp. 247-251

Author(s):

Ameer Hassoun ◽

Nessy Dahan ◽

Christopher Kelly

Keyword(s):

New York ◽

Case Reports ◽

Severe Disease ◽

Case Series ◽

Pediatric Emergency ◽

Rt Pcr ◽

Vulnerable Group ◽

Mild Disease ◽

Young Infants ◽

Novel Coronavirus

The emergence of novel coronavirus disease-2019 poses an unprecedented challenge to pediatricians. While the majority of children experience mild disease, initial case reports on young infants are conflicting. We present a case series of 8 hospitalized infants 60 days of age or younger with coronavirus disease-2019. A quarter of these patients had coinfections (viral or bacterial). None of these infants had severe disease. Continued vigilance in testing this vulnerable group of infants is warranted.

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SARS-CoV-2-Laden Respiratory Aerosol Deposition in the Lung Alveolar-Interstitial Region Is a Potential Risk Factor for Severe Disease: A Modeling Study

Journal of Personalized Medicine ◽

10.3390/jpm11050431 ◽

2021 ◽

Vol 11 (5) ◽

pp. 431

Author(s):

Sabine Hofer ◽

Norbert Hofstätter ◽

Albert Duschl ◽

Martin Himly

Keyword(s):

Risk Factor ◽

Particle Deposition ◽

Early Stage ◽

Severe Disease ◽

Ambient Air ◽

Aerosol Deposition ◽

Pulmonary Involvement ◽

Mild Disease ◽

Disease Initiation

COVID-19, predominantly a mild disease, is associated with more severe clinical manifestation upon pulmonary involvement. Virion-laden aerosols and droplets target different anatomical sites for deposition. Compared to droplets, aerosols more readily advance into the peripheral lung. We performed in silico modeling to confirm the secondary pulmonary lobules as the primary site of disease initiation. By taking different anatomical aerosol origins into consideration and reflecting aerosols from exhalation maneuvers breathing and vocalization, the physicochemical properties of generated respiratory aerosol particles were defined upon conversion to droplet nuclei by evaporation at ambient air. To provide detailed, spatially-resolved information on particle deposition in the thoracic region of the lung, a top-down refinement approach was employed. Our study presents evidence for hot spots of aerosol deposition in lung generations beyond the terminal bronchiole, with a maximum in the secondary pulmonary lobules and a high preference to the lower lobes of both lungs. In vivo, initial chest CT anomalies, the ground glass opacities, resulting from partial alveolar filling and interstitial thickening in the secondary pulmonary lobules, are likewise localized in these lung generations, with the highest frequency in both lower lobes and in the early stage of disease. Hence, our results suggest a disease initiation right there upon inhalation of virion-laden respiratory aerosols, linking the aerosol transmission route to pathogenesis associated with higher disease burden and identifying aerosol transmission as a new independent risk factor for developing a pulmonary phase with a severe outcome.

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Outpatient Management of COVID-19 Disease: A Holistic Patient-Centered Proposal Based on the Greek Experience

Journal of Personalized Medicine ◽

10.3390/jpm11080709 ◽

2021 ◽

Vol 11 (8) ◽

pp. 709

Author(s):

Adamantia Liapikou ◽

Eleni Tzortzaki ◽

Georgios Hillas ◽

Miltiadis Markatos ◽

Ilias C. Papanikolaou ◽

...

Keyword(s):

Preventive Measures ◽

Severe Disease ◽

Hospital Setting ◽

Guidance Document ◽

Outpatient Management ◽

Patient Centered ◽

Mild Disease ◽

Novel Coronavirus ◽

Second Wave ◽

Close Contacts

Novel coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic and affected more than 227 countries or territories, resulting in more than 179 million cases with over 3.890.00 deaths, as of June 25, 2021. The Hellenic Thoracic Society (HTS) during the second wave of COVID-19 pandemic released a guidance document for the management of patients with COVID-19 in the community and in hospital setting. In this review, with guidance the HTS document, we are discussing the outpatient management of COVID-19 patients, including the preventive measures, the patients’ isolation and quarantine criteria of close contacts, the severity and risk stratification, including the decisions for advanced hospitalization, and the disease management at home in patients with mild disease and after hospital discharge for those with more severe disease.

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