Boerhaave's syndrome after pentazocine-induced vomiting in a 21-year-old male with asthma: a case report.

Boerhaave's syndrome is an uncommon syndrome characterized by spontaneous rupture of the oesophagus with a high mortality rate. While excessive alcohol intake and binge-eating are the classic precipitants of this syndrome, medication-induced vomiting causing Booerhave's is quite uncommon. Traditionally managed operatively, conservative management is being increasingly reported in selected cases. We report the case of 21-year-old male with who developed sudden onset chest pain and dyspnoea after pentazocine induced vomiting. He was referred after lack of response to initial treatment for acute severe asthma. A chest CT scan showed pneumomediastinum, subcutaneous emphysema and oesophageal tear. He was managed conservatively with oxygen therapy, nil per mouth and antibiotics with improvement of symptoms and discharge after 8 days.

Respiratory Virus Infections in Asthma: Research Developments and Therapeutic Advances.

In this review, we discuss the latest developments in research pertaining to virus-induced asthma exacerbations and consider recent advances in treatment options. Asthma is a chronic disease of the airways that continues to impose a substantial clinical burden worldwide. Asthma exacerbations, characterised by an acute deterioration in respiratory symptoms and airflow obstruction, are associated with significant morbidity and mortality. These episodes are most commonly triggered by respiratory virus infections. The mechanisms underlying the pathogenesis of virus-induced exacerbations have been the focus of extensive biomedical research. Developing a robust understanding of the interplay between respiratory viruses and the host immune response will be critical for developing more efficacious, targeted therapies for exacerbations. CONCLUSION: There has been significant recent progress in our understanding of the mechanisms underlying virus-induced airway inflammation in asthma and these advances will underpin the development of future clinical therapies.

Sustained decrease in pediatric asthma emergency visits during the first year of the COVID-19 pandemic.

Background: On January 20, 2020, the first documented case of novel severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) was reported in the United States. The U.S. Centers for Disease Control and Prevention continues to report more morbidity and mortality in adults than in children. Early in Pandemic, there was a concern that patients with asthma would be affected disproportionately from COVID-19, but this was not manifested. It is now recognized that angiotensin-converting enzyme 2 receptors that are used by the coronavirus for infection have low expression in children with atopy that may contribute to decreased infectivity in children who are atopic. There are several early reports of decreased emergency department (ED) visits for children with asthma. The authors previously reported a decrease in pediatric ED visits in the spring of 2020, which correlated with school closure. Objective: To determine if this trend of decreased ED visits for pediatric asthma was sustained throughout the first COVID-19 pandemic year. Methods: ED data from one inner city children's hospital were collected by using standard medical claims codes. Conclusion: We reported a sustained year of decreased ED visits for children with asthma in one pediatric ED in an inner-city hospital; this seemed to be secondary to school closure and decreased exposure to upper respiratory infections.

Air quality, Environment and Respiratory Outcomes in Bronchopulmonary Dysplasia, the AERO-BPD cohort study: design and adaptation during the SARS-CoV-2 pandemic.

INTRODUCTION: Almost half of all school-age children with bronchopulmonary dysplasia (BPD) have asthma-like symptoms and more suffer from lung function deficits. While air pollution and indoor respiratory irritants are known to affect high-risk populations of children, few studies have objectively evaluated environmental contributions to long-term respiratory morbidity in this population. This study aimed to examine the role of indoor environmental exposures on respiratory morbidity in children with BPD. METHODS AND ANALYSIS: The Air quality, Environment and Respiratory Ouctomes in BPD (AERO-BPD) study is a prospective, single-centre observational study that will enrol a unique cohort of 240 children with BPD and carefully characterise participants and their indoor home environmental exposures. Measures of indoor air quality constituents will assess the relationship of nitrogen dioxide (NO2), particulate matter (PM2.5), nitric oxide (NO), temperature and humidity, as well as dust concentrations of allergens, with concurrently measured respiratory symptoms and lung function.Adaptations to the research protocol due to the SARS-CoV-2 pandemic included remote home environment and participant assessments. ETHICS AND DISSEMINATION: Study protocol was approved by the Boston Children's Hospital Committee on Clinical Investigation. Dissemination will be in the form of peer-reviewed publications and participant information products. TRIAL REGISTRATION NUMBER: NCT04107701.

Feasibility of an online platform delivery of pulmonary rehabilitation for individuals with chronic respiratory disease.

INTRODUCTION: SARS-CoV-2 has restricted access to face-to-face delivery of pulmonary rehabilitation (PR). Evidence suggests that telehealth-PR is non-inferior to outpatient PR. However, it is unknown whether patients who have been referred to face-to-face programmes can feasibly complete an online-PR programme. METHODS: This service evaluation used a mixed-methods approach to investigate a rapid PR service remodelling using the University of Gloucestershire eLearn Moodle platform. Quantitative baseline demographic and PR outcome data were collected from online-PR participants, and semistructured interviews were completed with PR staff and participants. RESULTS: Twenty-five individuals were eligible from a PR waiting list. Thirteen declined participation and 14 completed PR. Significant pre-post online PR improvements were achieved in 1 min sit-to-stand (CI 2.1 to 9 (p=0.004)), Generalised Anxiety Disorder (CI -0.3 to -2.6 (p=0.023)), Primary Health Questionnaire-9 (CI -0.3 to -5.1 (p=0.029)), Chronic Respiratory Questionnaire dyspnoea (CI 0.5 to 1.3 (p=0.001)), fatigue (CI 0.7 to 2 (p=0.0004)), emotion (CI 0.7 to 1.7 (p=0.0002)), mastery (CI 0.4 to 1.3 (p=0.001)). Interviews indicated that patient PR inclusion was made possible with digital support and a PR introduction session improved participant engagement and safety. Incremental progression of exercise was perceived as more successful online compared with face-to-face PR. However, perceptions were that education sessions were less successful. Online-PR required significant staff time resource. DISCUSSION: Online-PR improves patient outcomes and is feasible and acceptable for individuals referred for face-to-face PR in the context of a requirement for social distancing. Face-to-face programmes can be adapted in a rapid fashion with both staff and participants perceiving benefit. Future pragmatic trials are now warranted comparing online-PR including remote assessments to centre-based PR with suitably matched outcomes, and patient and staff perceptions sought regarding barriers and facilitators of online delivery.

Randomized, placebo controlled, double blinded pilot superiority phase 2 trial to evaluate the effect of curcumin in moderate to severe asthmatics.

BACKGROUND: Curcumin, a derivative of the spice turmeric, has been adopted by Eastern medicine for centuries as an adjunct to treat several medical conditions (e.g., anorexia and arthritis) because of its well-established anti-inflammatory properties. Studies have shown that the use of curcumin in mice models has led to reduction in several inflammatory markers as well as key inflammatory pathway enzymes. As a result, studies in Western medicine have developed to determine if this recognized benefit can be utilized for patients with inflammatory lung diseases, such as asthma. This study will seek to better understand if curcumin can be used as an adjunctive therapy for improving asthma control of patients with moderate to severe asthma; a finding we hope will allow for a more affordable treatment. METHODS: This study will utilize a randomized, placebo controlled, double blinded pilot superiority phase 2 trial at an outpatient pulmonary clinic in Southern California, USA. Subjects will be receiving Curcumin 1500 mg or matching placebo by mouth twice daily for the study period of 12 weeks. Subjects will be randomized to either a placebo or intervention Curcumin. Subjects will have 6 clinic visits: screening visit, a baseline visit, monthly clinic visits (weeks 4, 8, and 12), at weeks 4, 8, and a follow-up clinic visit or phone-call (week 16). Changes in asthma control test scores, number of days missed from school/work, FEV1 (% predicted), FEV1/FVC ratio, FVC (% predicted), blood eosinophil count, blood total IgE, and FeNO levels will be compared by group over time. DISCUSSION: The therapeutic effects of curcumin have been studied on a limited basis in asthmatics and has shown mixed results thus far. Our study hopes to further establish the benefits of curcumin, however, there are potential issues that may arise from our study design that we will address within this paper. Moreover, the onset of the COVID-19 pandemic has resulted in safety concerns that have delayed initiation of our study. This study will contribute to existing literature on curcumin's role in reducing lung inflammation as it presents in asthmatics as well as patients suffering from COVID-19. TRIAL REGISTRATION: This study protocol has been approved by the Institutional Review Board at Loma Linda University Health, (NCT04353310). IND# 145101 Registered April 20th, 2020. https://clinicaltrials.gov/ct2/show/NCT04353310 .

Revisiting pulmonary rehabilitation during COVID-19 pandemic: a narrative review.

There has been an apparent association between the risks of complications with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with a history of existing chronic respiratory diseases during the pandemic of coronavirus disease 2019 (COVID-19). SARS-CoV-2 poses a severe risk in cardiopulmonary management. Moreover, chronic respiratory diseases may further amplify the risk of morbidity and mortality among the afflicted population in the pandemic era. The present review outlines the importance of pulmonary rehabilitation (PR) in persons with chronic respiratory diseases (Chronic obstructive pulmonary disease (COPD) and Asthma) during the COVID-19 era. In this context, amongst the population with a pre-existing pulmonary diagnosis who have contracted SARS-CoV-2, following initial medical management and acute recovery, exercise-based pulmonary rehabilitation (PR) may play a crucial role in long-term management and recovery. The energy conservation techniques will play a pragmatic role in PR of mild to moderate severity cases to counter post-COVID-19 fatigue. Moreover, there is also an urgent need to effectively address post-COVID-19 anxiety and depression, affecting the PR delivery system.

Implications of preexisting asthma on COVID-19 pathogenesis.

The coronavirus disease 2019 (COVID-19) pandemic spreading at an alarming rate has taken a heavy toll on the public healthcare systems and economies worldwide. An abnormal and overactivated inflammatory response is occasionally elicited by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and this hyperinflammation is associated with worse prognosis of COVID-19. Theoretically, one would expect patients with asthma to be at a greater risk of SARS-CoV-2 infection considering their increased susceptibility to common respiratory virus-associated exacerbations. Surprisingly, current data do not consistently suggest an increased prevalence of asthma among patients with COVID-19. Considering the high global prevalence of asthma, the characteristics of the disease and/or their conventional therapy might play a role in their potential defense against COVID-19. This may be attributed to the T helper type 2 immune response predominantly seen in patients with asthma. Likewise, asthma therapeutics, including corticosteroids and biologics, may in fact benefit the patients with asthma by alleviating the development of hyperinflammation. On the other hand, elevated IL-17 levels are characteristically seen in a subset of asthma patients with severe disease as well as in patients with COVID-19. Targeting the IL-17 pathway as a treatment strategy could plausibly alleviate acute respiratory distress syndrome (ARDS) in patients with COVID-19 and asthma demonstrating a predominant T helper type 17 response. A clinical trial including a drug targeting this pathway may thus, constitute a logical addition to the global pursuit for effective therapeutics against COVID-19. The complex interplay between the asthma endotypes and COVID-19 is not very well understood and will be discussed in this mini-review.

Extracellular Vesicles and Asthma-More Than Just a Co-Existence.

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma.

Effect of comorbid pulmonary disease on the severity of COVID-19: A systematic review and meta-analysis.

Coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus 2 was first detected in Wuhan, China, in late 2019 and continues to spread worldwide. Persistent questions remain about the relationship between the severity of COVID-19 and comorbid diseases, as well as other chronic pulmonary conditions. In this systematic review and meta-analysis, we aimed to examine in detail whether the underlying chronic obstructive pulmonary diseases (COPD), asthma and chronic respiratory diseases (CRDs) were associated with an increased risk of more severe COVID-19. A comprehensive literature search was performed using five international search engines. In the initial search, 722 articles were identified. After eliminating duplicate records and further consideration of eligibility criteria, 53 studies with 658,073 patients were included in the final analysis. COPD was present in 5.2% (2191/42,373) of patients with severe COVID-19 and in 1.4% (4203/306,151) of patients with non-severe COVID-19 (random-effects model; OR = 2.58, 95% CI = 1.99-3.34, Z = 7.15, p < 0.001). CRD was present in 8.6% (3780/44,041) of patients with severe COVID-19 and in 5.7% (16,057/280,447) of patients with non-severe COVID-19 (random-effects model; OR = 2.14, 95% CI = 1.74-2.64, Z = 7.1, p < 0.001). Asthma was present in 2.3% (1873/81,319) of patients with severe COVID-19 and in 2.2% (11,796/538,737) of patients with non-severe COVID-19 (random-effects model; OR = 1.13, 95% CI = 0.79-1.60, Z = 0.66, p = 0.50). In conclusion, comorbid COPD and CRD were clearly associated with a higher severity of COVID-19; however, no association between asthma and severe COVID-19 was identified.

Evaluating the impact of coronavirus disease 2019 on asthma morbidity: A comprehensive analysis of potential influencing factors.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic period is experiencing better asthma control, fewer exacerbations, and health care utilization, with limited data on factors that could explain this phenomenon. OBJECTIVE: To confirm these improved asthma outcomes during COVID-19 and evaluate potential contributing factors. METHODS: In 18,912 pediatric patients with asthma treated in the Children's Hospital of Orange County network from 2017 to 2020, monthly asthma-related encounters and medication summaries were extracted from electronic health records, particulate matter 2.5 (PM2.5) air pollution from the California Air Resources Board, and influenza-like illness from Illness Surveillance Network for the first 6 months of each year. Changes in outcomes between January to March and April to June (post-COVID-19 shutdown in 2020) were compared with historical data using generalized estimating equations analyses for patient outcomes and generalized linear models for pollution exceedance, influenza-positive, and telehealth visit rates. RESULTS: During COVID-19, we found 78%, 90%, 68% reductions in hospitalization, emergency department visits, and exacerbations, respectively, compared with pre-COVID-19 2020, with significantly greater changes than the same time period of 2017 to 2019 and significant reductions in albuterol and inhaled corticosteroid use (P < .05). Emergency department visit reduction was not seen for African Americans. The PM2.5 and influenza rates were also significantly reduced during COVID-19 (P < .05). Increased rates in telehealth visits were greater in the publicly insured group when compared with commercially insured. CONCLUSION: Our data confirm reduced health care utilization and suggest better asthma control during COVID-19, except for African Americans. This was associated with a significant increase in telehealth visits and reductions in PM2.5 and influenza infections, but not better asthma controller adherence.

Unexpected decline in pediatric asthma morbidity during the coronavirus pandemic.

The Coronavirus disease 2019 (COVID-19) pandemic profoundly impacted health care utilization. We evaluated asthma-related emergency department (ED) and inpatient health care utilization by a county-specific Medicaid population, ages 2-18, during the COVID-19 pandemic and compared it to utilization from a 3-year average including 2017-2019. All-cause ED utilization and asthma medication fill rates were evaluated during the same timeframes. Relative to the 2017-2019 3-year average, cumulative asthma-related ED visits from January through June decreased by 45.8% (p = .03) and inpatient admission rates decreased by 50.5% (p = .03). The decline in asthma-related ED utilization was greater than the reduction of overall ED use during the same time period, suggesting that the decline involved factors specific to asthma and was not due solely to avoidance of health care facilities. Fill rates for asthma controller medications decreased during this time (p = .03) and quick relief medication fill rates had no significant change (p = .31). Multiple factors may have contributed to the decrease in acute asthma health care visits. Locally, decreased air pollution and viral exposures coincided with the "Stay-at-home" order in Ohio, and increased utilization of telehealth for assessment during exacerbations may have impacted outcomes. Identification of the cause of the decline in visit rates could spur new interventions to limit the need for ED and inpatient visits for asthma patients, leading to both economic and health-associated benefits.

Therapeutic targets in lung tissue remodelling and fibrosis.

Structural changes involving tissue remodelling and fibrosis are major features of many pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Abnormal deposition of extracellular matrix (ECM) proteins is a key factor in the development of tissue remodelling that results in symptoms and impaired lung function in these diseases. Tissue remodelling in the lungs is complex and differs between compartments. Some pathways are common but tissue remodelling around the airways and in the parenchyma have different morphologies. Hence it is critical to evaluate both common fibrotic pathways and those that are specific to different compartments; thereby expanding the understanding of the pathogenesis of fibrosis and remodelling in the airways and parenchyma in asthma, COPD and IPF with a view to developing therapeutic strategies for each. Here we review the current understanding of remodelling features and underlying mechanisms in these major respiratory diseases. The differences and similarities of remodelling are used to highlight potential common therapeutic targets and strategies. One central pathway in remodelling processes involves transforming growth factor (TGF)-ß induced fibroblast activation and myofibroblast differentiation that increases ECM production. The current treatments and clinical trials targeting remodelling are described, as well as potential future directions. These endeavours are indicative of the renewed effort and optimism for drug discovery targeting tissue remodelling and fibrosis.

Clinical presentation and outcomes of the first patients with COVID-19 in Argentina: Results of 207079 cases from a national database.

BACKGROUND: There is limited evidence on the clinical characteristics of SARS-CoV-2 infection in Latin America. We present findings from a nationwide study in Argentina. RESEARCH QUESTION: What is disease severity measures and risk factors are associated with admission to an intensive care unit and mortality? STUDY DESIGN AND METHODS: Data were extracted from the COVID-19 database of the Integrated Argentina Health Information System, encompassing the period of March 3rd to October 2nd, 2020, using a standardized case report form that included information on contact history, clinical signs and symptoms, and clinical diagnosis. Information was collected at the initial site of care and follow-up conducted through calls by the regional healthcare authorities. A confirmed case of COVID-19 was defined as having a positive result through sequencing or real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. RESULTS: RT-PCR testing was positive in 738,776 cases. Complete datasets were available for analysis in 207,079 cases. Mean age was 42.9±18.8 years, 50.0% were males. Frequent co-existing conditions included hypertension (19.2%), diabetes (9.7%), asthma (6.1%) and obesity (5.2%). Most common symptoms included fever (58.5%), cough (58.0%), headache (45.4%), and sore throat (42.1%). Death or ICU admission were independently associated with older age, male, coma, dyspnea or tachypnea, and seizures, with underlying co-morbidities such as immunodeficiency, chronic renal failure, and liver disease showing the strongest effects. INTERPRETATION: Most cases of COVID-19 diagnosed in Argentina were mild and had a favorable outcome, but fatality rates were relatively elevated. Risk factors for adverse outcome included older age, male sex, coma and seizures, and the concurrent presence of several morbidities. These data may be useful for healthcare providers and healthcare policy makers of low-middle income and Latin American countries to guide decisions toward optimized care during the pandemic.

Annual SO2 exposure, asthma, atopy, and lung function in Puerto Rican children.

BACKGROUND: Long-term effects of sulfur dioxide (SO2 ) exposure on children, a vulnerable population, are largely unknown. Further, how long-term SO2 affects Puerto Rican children living in the island of Puerto Rico, a group with high asthma prevalence, is unclear. We evaluated the effects of annual average 1-hour daily maximum SO2 average on asthma, atopy, total immunoglobulin E (IgE), and lung function in Puerto Rican children. METHODS: A cohort of 678 children (351 with asthma, 327 without asthma) was recruited in Puerto Rico from 2009 to 2010. Annual average 1-hour daily maximum SO2 exposure was interpolated utilizing publicly available monitoring data. Multivariable logistic and linear regression was used for the analysis of asthma, atopy (defined as an IgE ≥0.35 IU/mL to at least one of five common aero-allergens), total IgE, and lung function measures (forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1], and FEV1/FVC ratio). RESULTS: Annual SO2 exposure (per 1 ppb) was significantly associated with asthma (odds ratio [OR] = 1.42; 95% confidence interval [CI] = 1.05-1.91) and atopy (OR = 1.35; 95% CI = 1.02-1.78). Such exposure was also significantly associated with lower FEV1/FVC in all children (ß = -1.42; 95% CI = -2.78 to -0.08) and in children with asthma (ß = -2.39; 95% CI= -4.31 to -0.46). Annual SO2 exposure was not significantly associated with total IgE, FEV1, or FVC. CONCLUSIONS: Among Puerto Rican children in Puerto Rico, long-term SO2 exposure is linked to asthma and atopy. In these children, long-term SO2 exposure is also associated with reduced FEV1/FVC, particularly in those with asthma.

Addressing Reduced Laboratory-Based Pulmonary Function Testing During a Pandemic.

To reduce the spread of the severe acute respiratory syndrome coronavirus 2, many pulmonary function testing (PFT) laboratories have been closed or have significantly reduced their testing capacity. Because these mitigation strategies may be necessary for the next 6 to 18 months to prevent recurrent peaks in disease prevalence, fewer objective measurements of lung function will alter the diagnosis and care of patients with chronic respiratory diseases. PFT, which includes spirometry, lung volume, and diffusion capacity measurement, is essential to the diagnosis and management of patients with asthma, COPD, and other chronic lung conditions. Both traditional and innovative alternatives to conventional testing must now be explored. These may include peak expiratory flow devices, electronic portable spirometers, portable exhaled nitric oxide measurement, airwave oscillometry devices, and novel digital health tools such as smartphone microphone spirometers and mobile health technologies along with integration of machine learning approaches. The adoption of some novel approaches may not merely replace but could improve existing management strategies and alter common diagnostic paradigms. With these options comes important technical, privacy, ethical, financial, and medicolegal barriers that must be addressed. However, the coronavirus disease 19 pandemic also presents a unique opportunity to augment conventional testing by including innovative and emerging approaches to measuring lung function remotely in patients with respiratory disease. The benefits of such an approach have the potential to enhance respiratory care and empower patient self-management well beyond the current global pandemic.

Reduced risk of COVID-19 hospitalization in asthmatic and COPD patients: a benefit of inhaled corticosteroids?

Background: The comorbidities and clinical signs of coronavirus disease 2019 (COVID-19) patients have been reported mainly as descriptive statistics, rather than quantitative analysis even in very large investigations. The aim of this study was to identify specific patients' characteristics that may modulate COVID-19 hospitalization risk.Research design and methods: A pooled analysis was performed on high-quality epidemiological studies to quantify the prevalence (%) of comorbidities and clinical signs in hospitalized COVID-19 patients. Pooled data were used to calculate the relative risk (RR) of specific comorbidities by matching the frequency of comorbidities in hospitalized COVID-19 patients with those of general population.Results: The most frequent comorbidities were hypertension, diabetes mellitus, and cardiovascular and/or cerebrovascular diseases. The RR of COVID-19 hospitalization was significantly (P < 0.05) reduced in patients with asthma (0.86, 0.77-0.97) or chronic obstructive pulmonary disease (COPD) (0.46, 0.40-0.52). The most frequent clinical signs were fever and cough.Conclusion: The clinical signs of hospitalized COVID-19 patients are similar to those of other infective diseases. Patients with asthma or COPD were at lower hospitalization risk. This paradoxical evidence could be related with the protective effect of inhaled corticosteroids that are administered worldwide to most asthmatic and COPD patients.