Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease and is presumed to be central to the altered responsiveness to recurrent infection in these patients. We examined ...the effects of smoke priming underlying the exacerbated response to viral infection in mice. Lack of interleukin-33 (IL-33) signaling conferred complete protection during exacerbation and prevented enhanced inflammation and exaggerated weight loss. Mechanistically, smoke was required to upregulate epithelial-derived IL-33 and simultaneously alter the distribution of the IL-33 receptor ST2. Specifically, smoke decreased ST2 expression on group 2 innate lymphoid cells (ILC2s) while elevating ST2 expression on macrophages and natural killer (NK) cells, thus altering IL-33 responsiveness within the lung. Consequently, upon infection and release, increased local IL-33 significantly amplified type I proinflammatory responses via synergistic modulation of macrophage and NK cell function. Therefore, in COPD, smoke alters the lung microenvironment to facilitate an alternative IL-33-dependent exaggerated proinflammatory response to infection, exacerbating disease.
•IL-33 is upregulated by cigarette smoke and released in response to virus infection•Smoke dampens ST2 expression on ILC2s but enhances ST2 on NK cells and macrophages•IL-33 drives an exacerbated Th1-cell-like inflammatory response to virus infection•IL-33 might play a critical role in pathogen-induced exacerbations of COPD
Smoking is thought to be central to the altered responsiveness to infection in patients with chronic obstructive pulmonary disease (COPD). Humbles and colleagues show that mice lacking interleukin-33 (IL-33) are protected from smoke-induced exaggerated inflammatory responses to virus infection, suggesting that IL-33 is a critical mediator in acute exacerbations of COPD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Despite substantial progress in reducing the global impact of many non-communicable diseases, including heart disease and cancer, morbidity and mortality due to chronic respiratory disease continues ...to increase. Many factors have contributed to what must now be considered a public health emergency: failure to limit the sale and consumption of tobacco products, unchecked exposure to environmental pollutants across the life course, and the ageing of the global population (partly as a result of improved outcomes for other conditions). In particular, we advocate for: broader understanding of risk factors (including the devastating effects of global poverty) and the preventive measures necessary to avoid future cases of COPD, disruptive approaches to diagnosis that are not solely based on spirometric airflow limitation but also involve identification of early pathological changes that are more amenable to reversal, classification of the disease into types that share pathophysiological similarities and could lead to novel preventive and therapeutic approaches, and a new approach to the diagnosis and assessment of exacerbations of COPD that focuses on disease mechanisms. An acute worsening of COPD is termed an exacerbation, and such episodes account for a substantial proportion of the attributable cost of the disease and are associated with accelerated lung function loss, prolonged impairments in quality of life, and similar prognosis to many stage III or IV solid organ malignancies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To develop predictive criteria for COVID-19-associated cytokine storm (CS), a severe hyperimmune response that results in organ damage in some patients infected with COVID-19. We hypothesised that ...criteria for inflammation and cell death would predict this type of CS.
We analysed 513 hospitalised patients who were positive for COVID-19 reverse transcriptase PCR and for ground-glass opacity by chest high-resolution CT. To achieve an early diagnosis, we analysed the laboratory results of the first 7 days of hospitalisation. We implemented logistic regression and principal component analysis to determine the predictive criteria. We used a 'genetic algorithm' to derive the cut-offs for each laboratory result. We validated the criteria with a second cohort of 258 patients.
We found that the criteria for macrophage activation syndrome, haemophagocytic lymphohistiocytosis and the HScore did not identify the COVID-19 cytokine storm (COVID-CS). We developed new predictive criteria, with sensitivity and specificity of 0.85 and 0.80, respectively, comprising three clusters of laboratory results that involve (1) inflammation, (2) cell death and tissue damage, and (3) prerenal electrolyte imbalance. The criteria identified patients with longer hospitalisation and increased mortality. These results highlight the relevance of hyperinflammation and tissue damage in the COVID-CS.
We propose new early predictive criteria to identify the CS occurring in patients with COVID-19. The criteria can be readily used in clinical practice to determine the need for an early therapeutic regimen, block the hyperimmune response and possibly decrease mortality.
In this trial evaluating mepolizumab, an anti–interleukin-5 antibody, the rate of COPD exacerbations among patients whose COPD was characterized by an increased number of eosinophils in the ...circulating blood was lower with mepolizumab than with placebo.
Spontaneous pneumothorax is an uncommon complication of COVID-19 viral pneumonia. The exact incidence and risk factors are still unknown. Herein we review the incidence and outcomes of pneumothorax ...in over 3000 patients admitted to our institution for suspected COVID-19 pneumonia.
We performed a retrospective review of COVID-19 cases admitted to our hospital. Patients who were diagnosed with a spontaneous pneumothorax were identified to calculate the incidence of this event. Their clinical characteristics were thoroughly documented. Data regarding their clinical outcomes were gathered. Each case was presented as a brief synopsis.
Three thousand three hundred sixty-eight patients were admitted to our institution between March 1st, 2020 and June 8th, 2020 for suspected COVID 19 pneumonia, 902 patients were nasopharyngeal swab positive. Six cases of COVID-19 patients who developed spontaneous pneumothorax were identified (0.66%). Their baseline imaging showed diffuse bilateral ground-glass opacities and consolidations, mostly in the posterior and peripheral lung regions. 4/6 cases were associated with mechanical ventilation. All patients required placement of a chest tube. In all cases, mortality (66.6%) was not directly related to the pneumothorax.
Spontaneous pneumothorax is a rare complication of COVID-19 viral pneumonia and may occur in the absence of mechanical ventilation. Clinicians should be vigilant about the diagnosis and treatment of this complication.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Precision medicine is a patient-specific approach that integrates all relevant clinical, genetic and biological information in order to optimise the therapeutic benefit relative to the possibility of ...side-effects for each individual. Recent clinical trials have shown that higher blood eosinophil counts are associated with a greater efficacy of inhaled corticosteroids (ICSs) in chronic obstructive pulmonary disease (COPD) patients. Blood eosinophil counts are a biomarker with potential to be used in clinical practice, to help target ICS treatment with more precision in COPD patients with a history of exacerbations despite appropriate bronchodilator treatment.The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 pharmacological treatment algorithms, based on the ABCD assessment, can be applied relatively easily to treatment-naive individuals at initial presentation. However, their use is more problematic during follow-up in patients who are already on maintenance treatment. There is a need for a different system to guide COPD pharmacological management during follow-up.Recent large randomised controlled trials have provided important new information concerning the therapeutic effects of ICSs and long-acting bronchodilators on exacerbations. The new evidence regarding blood eosinophils and inhaled treatments, and the need to distinguish between initial and follow-up pharmacological management, led to changes in the GOLD pharmacological treatment recommendations. This article explains the evidence and rationale for the GOLD 2019 pharmacological treatment recommendations.
Patients with advanced lung disease, especially patients with COPD, suffer from dyspnea at rest that worsens during the performance of even limited physical activities. The causes of dyspnea are ...multifactorial and are related to structural changes found in the parenchymal compartment of the lung as well as the airway and pulmonary vasculature. Alterations in any of the lung compartments may have negative consequences for the physiological performance of exercise. Respiratory assist devices that attenuate the pathophysiological derangements induced by the underlying lung disease, and/or unload the increased work of breathing, can enhance the performance of exercise, and help to produce more robust training effects in patients with lung disease. Herein we review the data that examines these approaches using respiratory assist devices to improve exercise outcomes in patients with COPD.
Global Initiative for Chronic Obstructive Lung Disease 2023 Report (GOLD) has published the complete 2023 GOLD report, which can be freely downloaded from its web page a "pocket guide" and a ..."teaching slide set". It contains important changes compared to earlier versions, and incorporates 387 new references. Here, Agusti et al present an executive summary of this GOLD 2023 report that summarizes aspects that are relevant from a clinician's perspective and updates evidence published since the prior executive summary in 2017.
In patients with moderate to very severe COPD and a blood eosinophil count of 220 cells per cubic millimeter or greater, treatment with benralizumab, an anti–interleukin-5 receptor antibody ...(administered at doses similar to or higher than those used for severe asthma) did not change the rate of COPD exacerbations.
This Executive Summary of the Global Strategy for the Diagnosis, Management, and Prevention of COPD (GOLD) 2017 Report focuses primarily on the revised and novel parts of the document. The most ...significant changes include: 1) the assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation. ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations; 2) for each of the groups A to D, escalation strategies for pharmacological treatments are proposed; 3) the concept of de-escalation of therapy is introduced in the treatment assessment scheme; 4) nonpharmacologic therapies are comprehensively presented and; 5) the importance of comorbid conditions in managing COPD is reviewed.
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