Many patients with an idiopathic interstitial pneumonia (IIP) have clinical features that suggest an underlying autoimmune process but do not meet established criteria for a connective tissue disease (CTD). Researchers have proposed differing criteria and terms to describe these patients, and lack of consensus over nomenclature and classification limits the ability to conduct prospective studies of a uniform cohort.The "European Respiratory Society/American Thoracic Society Task Force on Undifferentiated Forms of Connective Tissue Disease-associated Interstitial Lung Disease" was formed to create consensus regarding the nomenclature and classification criteria for patients with IIP and features of autoimmunity.The task force proposes the term "interstitial pneumonia with autoimmune features" (IPAF) and offers classification criteria organised around the presence of a combination of features from three domains: a clinical domain consisting of specific extra-thoracic features, a serologic domain consisting of specific autoantibodies, and a morphologic domain consisting of specific chest imaging, histopathologic or pulmonary physiologic features.A designation of IPAF should be used to identify individuals with IIP and features suggestive of, but not definitive for, a CTD. With IPAF, a sound platform has been provided from which to launch the requisite future research investigations of a more uniform cohort. @ERSpublications ERS/ATS task force provides nomenclature and classification criteria for patients with IIP and autoimmune features
The involvement of adenosine A 1 and A 2A receptors in the motor effects of caffeine is still a matter of debate. In the present study, counteraction of the motor-depressant effects of the selective A 1 receptor agonist CPA and the A 2A receptor agonist CGS 21680 by caffeine, the selective A 1 receptor antagonist CPT, and the A 2A receptor antagonist MSX-3 was compared. CPT and MSX-3 produced motor activation at the same doses that selectively counteracted motor depression induced by CPA and CGS 21680, respectively. Caffeine also counteracted motor depression induced by CPA and CGS 21680 at doses that produced motor activation. However, caffeine was less effective than CPT at counteracting CPA and even less effective than MSX-3 at counteracting CGS 21680. On the other hand, when administered alone in habituated animals, caffeine produced stronger motor activation than CPT or MSX-3. An additive effect on motor activation was obtained when CPT and MSX-3 were coadministered. Altogether, these results suggest that the motoractivating effects of acutely administered caffeine in rats involve the central blockade of both A 1 and A 2A receptors. Chronic exposure to caffeine in the drinking water (1.0 mg/ml) resulted in tolerance to the motor effects of an acute administration of caffeine, lack of tolerance to amphetamine, apparent tolerance to MSX-3 (shift to the left of its 'bell-shaped' dose-response curve), and true crosstolerance to CPT. The present results suggest that development of tolerance to the effects of A 1 receptor blockade might be mostly responsible for the tolerance to the motor-activating effects of caffeine and that the residual motor-activating effects of caffeine in tolerant individuals might be mostly because of A 2A receptor blockade.
BackgroundThe major reasons to treat sarcoidosis are to lower the morbidity and mortality risk or to improve quality of life (QoL). The indication for treatment varies depending on which manifestation is the cause of symptoms: lungs, heart, brain, skin, or other manifestations. While glucocorticoids (GC) remain the first choice for initial treatment of symptomatic disease, prolonged use is associated with significant toxicity. GC-sparing alternatives are available. The presented treatment guideline aims to provide guidance to physicians treating the very heterogenous sarcoidosis manifestations.Materials and MethodsA European Respiratory Society Task Force (TF) committee composed of clinicians, methodologists, and patients with experience in sarcoidosis developed recommendations based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology. The committee developed eight PICO (Patients, Intervention, Comparison, Outcomes) questions and these were used to make specific evidence-based recommendations.ResultsThe TF committee delivered twelve recommendations for seven PICOs. These included treatment of pulmonary, cutaneous, cardiac, and neurologic disease as well as fatigue. One PICO question regarding small fiber neuropathy had insufficient evidence to support a recommendation. In addition to the recommendations, the committee provided information on how they use alternative treatments, when there was insufficient evidence to support a recommendation.ConclusionsThere are many treatments available to treat sarcoidosis. Given the diverse nature of the disease, treatment decisions require an assessment of organ involvement, risk for significant morbidity, and impact on QoL of the disease and treatment.MessageAn evidence based guideline for treatment of sarcoidosis is presented. The panel used the GRADE approach and specific recommendations are made. A major factor in treating patients is the risk of loss of organ function or impairment of quality of life.
These data suggest that sarcoidosis and idiopathic pulmonary fibrosis are the most frequent ILDs in our population. In comparison with the few previous reports, interesting dissimilarities have been observed.
Pulmonary fibrosis is the end stage of many diffuse parenchymal lung diseases. It is characterised by excessive matrix formation leading to destruction of the normal lung architecture and finally death. Despite an exponential increase in our understanding of potentially important mediators and mechanisms, the delineation of primary pathways has proven to be elusive.In this review susceptibility and injurious agents, such as viruses and gastro-oesophageal reflux, and their probable role in initiating disease will be discussed. Further topics that are elaborated are candidate ancillary pathways, including immune mechanisms, oxidative and endoplasmic reticulum stress, activation of the coagulation cascade and the potential role of stem cells. This review will try to provide the reader with an integrated view on the current knowledge and attempts to provide a road map for future research.It is important to explore robust models of overall pathogenesis, reconciling a large number of clinical and scientific observations. We believe that the integration of current data into a ''big picture'' overview of fibrogenesis is essential for the development of effective antifibrotic strategies. The latter will probably consist of a combination of agents targeting a number of key pathways.
IntroductionHospitalised patients with coronavirus disease 19 (COVID-19) as a result of SARS-CoV-2 infection have a high mortality rate and frequently require non-invasive respiratory support or invasive ventilation. Optimising and standardising management through evidence-based guidelines may improve quality of care and therefore patient outcomes.MethodsA task force from the European Respiratory Society and endorsed by the Chinese Thoracic Society identified priority interventions (pharmacological and non-pharmacological) for the initial version of this “living guideline” using the PICO (population, intervention, comparator, outcome) format. The GRADE approach was used for assessing the quality of evidence and strength of recommendations. Systematic literature reviews were performed, and data pooled by meta-analysis where possible. Evidence tables were presented and evidence to decision frameworks were used to formulate recommendations.ResultsBased on the available evidence at the time of guideline development (February 20th, 2021) the panel makes a strong recommendation in favour of the use of systemic corticosteroids in patients requiring supplementary oxygen or ventilatory support, and for the use of anticoagulation in hospitalised patients. The panel makes a conditional recommendation for IL-6 receptor antagonist monoclonal antibody treatment and high flow nasal oxygen or continuous positive airway pressure in patients with hypoxaemic respiratory failure. The panel make strong recommendations against the use of hydroxychloroquine and lopinavir-ritonavir. Conditional recommendations are made against the use of azithromycin, hydroxychloroquine and azithromycin, colchicine, and remdesivir, in the latter case specifically in patients requiring invasive mechanical ventilation. No recommendation was made for remdesivir in patients requiring supplemental oxygen. Further recommendations for research are made.ConclusionThe evidence base for management of COVID-19 now supports strong recommendations in favour and against specific interventions. These guidelines will be regularly updated as further evidence becomes available.
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