Radiation-induced lung injury (RILI) encompasses any lung toxicity induced by radiation therapy (RT) and manifests acutely as radiation pneumonitis and chronically as radiation pulmonary fibrosis. ...Because most patients with thoracic and breast malignancies are expected to undergo RT in their lifetime, many with curative intent, the population at risk is significant. Furthermore, indications for thoracic RT are expanding given the advent of stereotactic body radiation therapy (SBRT) or stereotactic ablative radiotherapy (SABR) for early-stage lung cancer in nonsurgical candidates as well as oligometastatic pulmonary disease from any solid tumor. Fortunately, the incidence of serious pulmonary complications from RT has decreased secondary to advances in radiation delivery techniques. Understanding the temporal relationship between RT and injury as well as the patient, disease, and radiation factors that help distinguish RILI from other etiologies is necessary to prevent misdiagnosis. Although treatment of acute pneumonitis is dependent on clinical severity and typically responds completely to corticosteroids, accurately diagnosing and identifying patients who may progress to fibrosis is challenging. Current research advances include high-precision radiation techniques, an improved understanding of the molecular basis of RILI, the development of small and large animal models, and the identification of candidate drugs for prevention and treatment.
Dyspnea is a distressing, debilitating, and near-ubiquitous symptom affecting patients with COPD. In addition to the functional consequences of dyspnea, which include activity limitation and reduced ...exercise tolerance, it is important to consider its psychological impact on patients with COPD, such as onset of depression or anxiety. Moreover, the anticipation of dyspnea itself can have a significant effect on patients' emotions and behavior, with patients frequently self-limiting physical activity to avoid what has become the hallmark symptom of COPD. Dyspnea is, therefore, a key target for COPD treatments. Pharmacologic treatments can optimize respiratory mechanics, provide symptom relief, and reduce patients' increased inspiratory neural drive to breathe. However, it is important to acknowledge the value of non-pharmacologic interventions, such as pulmonary rehabilitation and patient self-management education, which have proven to be invaluable tools for targeting the affective components of dyspnea. Furthermore, it is important to encourage maintenance of physical activity to optimize long-term patient outcomes. Here, we review the physiological and psychological consequences of activity-related dyspnea in COPD, assess the efficacy of modern management strategies in improving this common respiratory symptom, and discuss key unmet clinical and research needs that warrant further immediate attention.
Immunological biomarkers in severe asthma Narendra, Dharani; Blixt, John; Hanania, Nicola A.
Seminars in immunology,
December 2019, 2019-12-00, 20191201, Letnik:
46
Journal Article
Recenzirano
•Asthma is a heterogeneous disease with several phenotypes and endotypes and Biomarkers help in the phenotyping and endotyping of asthma.•Biomarkers should be clinically applicable and act as ...surrogate markers to reflect disease mechanisms, predict the course of disease, and response to certain therapies.•Only few biomarkers that reflect T2 airway inflammation are currently readily available for clinical use.•There is a great unmet need for biomarkers reflecting T2-Low asthma.•Use of composite biomarkers may prove to be of greater importance than a single biomarkers but that needs further evaluation.
Severe asthma is heterogeneous in its clinical presentation, underlying pathophysiology, course and response to therapy. Clinical and physiological assessment of severe asthma is often inadequate in predicting underlying disease mechanisms and or response to medications. With the emergence of novel targeted therapies in severe asthma, the need for reproducible, easily measured biomarkers became obvious but only few are currently available for clinical use. These biomarkers along with the clinical presentation of the patient play an important role in identifying phenotypes and endotypes, predicting the clinical course and prognosis and improving the precision therapeutic approach to asthma.
Asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) or without (CRSsNP) are chronic respiratory diseases. These two disorders often co-exist based on common anatomical, immunological, ...histopathological, and pathophysiological basis. Usually, asthma with comorbid CRSwNP is driven by type 2 (T2) inflammation which predisposes to more severe, often intractable, disease. In the past two decades, innovative technologies and detection techniques in combination with newly introduced targeted therapies helped shape our understanding of the immunological pathways underlying inflammatory airway diseases and to further identify several distinct clinical and inflammatory subsets to enhance the development of more effective personalized treatments. Presently, a number of targeted biologics has shown clinical efficacy in patients with refractory T2 airway inflammation, including anti-IgE (omalizumab), anti-IL-5 (mepolizumab, reslizumab)/anti-IL5R (benralizumab), anti-IL-4R-α (anti-IL-4/IL-13, dupilumab), and anti-TSLP (tezepelumab). In non-type-2 endotypes, no targeted biologics have consistently shown clinical efficacy so far. Presently, multiple therapeutical targets are being explored including cytokines, membrane molecules and intracellular signalling pathways to further expand current treatment options for severe asthma with and without comorbid CRSwNP. In this review, we discuss existing biologics, those under development and share some views on new horizons.
Summary Asthma and COPD are two chronic inflammatory disorders of the airway characterized by airflow limitation. While many similarities exist between these two diseases, they are pathologically ...distinct due to the involvement of different inflammatory cells; predominantly neutrophils, CD8 lymphocytes in COPD and eosinophils and CD4 lymphocytes in asthma. Cigarette smoking is associated with accelerated decline of lung function, increased mortality, and worsening of symptoms in both asthma and COPD. Furthermore, exposure to cigarette smoke can alter the inflammatory mechanisms in asthma to become similar to that seen in COPD with increasing CD8 cells and neutrophils and may therefore alter the response to therapy. Cigarette smoke exposure has been associated with a poor response to inhaled corticosteroids which are recommended as first line anti-inflammatory medications in asthma and as an add-on therapy in patients with severe COPD with history of exacerbations. While the main proposed mechanism for this altered response is the reduction of the histone deacetylase 2 (HDAC2) enzyme system, other possible mechanisms include the overexpression of GR-β, activation of p38 MAPK pathway and increased production of inflammatory cytokines such as IL-2, 4, 8, TNF-α and NF-Kß. Few clinical trials suggest that leukotriene modifiers may be an alternative to corticosteroids in smokers with asthma but there are currently no drugs which effectively reduce the progression of inflammation in smokers with COPD. However, several HDAC2 enhancers including low dose theophylline and other potential anti-inflammatory therapies including PDE4 inhibitors and p38 MAPK inhibitors are being evaluated.
Asthma exacerbations can be life-threatening, with 25,000 to 50,000 such patients per year requiring admission to an ICU in the United States. Appropriate triage of life-threatening asthma is ...dependent on both static assessment of airway function and dynamic assessment of response to therapy. Treatment strategies focus on achieving effective bronchodilation with inhaled β
-agonists, muscarinic antagonists, and magnesium sulphate while reducing inflammation with systemic corticosteroids. Correction of hypoxemia and hypercapnia, a key in managing life-threatening asthma, occasionally requires the incorporation of noninvasive mechanical ventilation to decrease the work of breathing. Endotracheal intubation and mechanical ventilation should not be delayed if clinical improvement is not achieved with conservative therapies. However, mechanical ventilation in these patients often requires controlled hypoventilation, adequate sedation, and occasional use of muscle relaxation to avoid dynamic hyperinflation, which can result in barotrauma or volutrauma. Sedation with ketamine or propofol is preferred because of their potential bronchodilation properties. In this review, we outline strategies for the assessment and management of patients with acute life-threatening asthma focusing on those requiring admission to the ICU.
We examined the validity and responsiveness of the Depression Anxiety and Stress Scales-21 (DASS-21) in patients with COPD following an 8-week pulmonary rehabilitation program (PRP).
Five hundred and ...fifty-seven patients with clinically stable COPD completed an 8-week outpatient multidisciplinary PRP, comprising 2 h (1 h of exercise and 1 h of education) per week. Anxiety, exercise capacity, quality of life, and dyspnea were measured pre- and post-PRP, utilizing the Anxiety Inventory for Respiratory Disease, Incremental Shuttle Walk Test, St. George’s Respiratory Questionnaire, and modified Medical Research Council dyspnea scale, respectively. In addition, we administered the DASS-21 to assess both the validity and responsiveness of this tool compared with other, well-established metrics.
The mean (SD) age of participants was 71.6 (9.4) years, and 49% were women. The DASS-21 reflected responsiveness to pulmonary rehabilitation. Among participants with a high depression score (> 9), the depression subscale score fell from 18.62 pre-PRP to 13.12 post-PRP (P < .001). Similarly, among participants with a high anxiety score (> 7), the anxiety subscale fell from 14.60 pre-PRP to 10.99 post-PRP (P < .001). Likewise, among participants with a high stress score (> 14), the stress subscale score fell from 23.51 pre-PRP to 16.34 post-PRP (P < .001). Among these subsamples, the effect size was medium at 0.49 for depression and 0.54 for anxiety, and large at 0.81 for stress. The change in DASS-21 subset (depression, anxiety, and stress) correlated with the change in total SGRQ score, at P < .001.
The DASS-21 has acceptable validity and is a responsive scale for use in PRP in patients with COPD.
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