Dexamethasone in patients hospitalized with COVID-19: Whether, when and to whom

A clinical interpretation of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) study was performed to provide a useful tool to understand whether, when, and to whom dexamethasone should be administered during hospitalization for COVID-19. A post hoc analysis of data published in the preliminary report of the RECOVERY study was performed to calculate the person-based number needed to treat (NNT) and number needed to harm (NNH) of 6 mg dexamethasone once daily for up to 10 days vs. usual care with respect to mortality. At day 28, the NNT of dexamethasone vs. usual care was 36.0 (95%CI 24.9–65.1, p < 0.05) in all patients, 8.3 (95%CI 6.0–13.1, p < 0.05) in patients receiving invasive mechanical ventilation, and 34.6 (95%CI 22.1–79.0, p < 0.05) in patients receiving oxygen only (with or without noninvasive ventilation). Dexamethasone increased mortality compared with usual care in patients not requiring oxygen supplementation, leading to a NNH value of 26.7 (95%CI 18.1–50.9, p < 0.05). NNT of dexamethasone vs. usual care was 17.3 (95%CI 14.9–20.6) in subjects <70 years, 27.0 (95%CI 18.5–49.8) in men, and 16.2 (95%CI 13.2–20.8) in patients in which the onset of symptoms was >7 days. Dexamethasone is effective in male subjects < 70 years that require invasive mechanical ventilation experiencing symptoms from >7 days and those patients receiving oxygen without invasive mechanical ventilation; it should be avoided in patients not requiring respiratory support

cost of walking exertional dyspnoea and fatigue in individuals with multiple sclerosis not requiring assistive devices

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SARS-CoV-2 infection in patients with cystic fibrosian overwiew

The novel coronavirus SARS-CoV-2 was first identified in China in December 2019 and has since spread worldwide. People with Cystic Fibrosis (CF) have reduced survival mainly because of respiratory failure due to chronic pulmonary infections. Therefore, CF patients should be considered to have an increased risk of developing severe manifestations in case of SARS-CoV-2 infection. Surprisingly, the results of recent studies concerning SARS-CoV-2 infection in patients with CF show that in these patients the infection rate was lower than that of the general population. Various factors have been considered to explain a possible protective effect of CF against SARS-CoV-2 infection

Oral corticosteroids dependence and biologic drugs in severe asthma: Myths or facts? a systematic review of real‐world evidence

Airway inflammation represents an important characteristic in asthma, modulating airflow limitation and symptom control, and triggering the risk of asthma exacerbation. Thus, although corticosteroids represent the cornerstone for the treatment of asthma, severe patients may be dependent on oral corticosteroids (OCSs). Fortunately, the current humanised monoclonal antibodies (mAbs) benralizumab, dupilumab, mepolizumab, omalizumab, and reslizumab have been proven to induce an OCS‐sparing effect in randomized controlled trials (RCTs), thus overcoming the problem of OCS dependence in severe asthma. Nevertheless, a large discrepancy has been recognized between selected patients enrolled in RCTs and non‐selected asthmatic populations in real‐world settings. It is not possible to exclude that the OCS‐sparing effect of mAbs resulting from the RCTs could be different than the real effect resulting in clinical practice. Therefore, we performed a systematic review and correlation analysis to assess whether mAbs are effective in eliciting an OCS‐sparing effect and overcoming the OCS dependence in severe asthmatic patients in real‐world settings. Overall, real‐world studies support the evidence that OCS dependence is a real condition that, however, can be found only in a small number of really severe asthmatic patients. In most patients, the dependence on OCS can be related to modifying factors that, when adequately modulated, may lead to a significant reduction or suspension of OCS maintenance. Conversely, in severe asthmatics in whom OCS resistance is proved by a high daily dose intake, mAbs allow reversion of the OCS dependence, leading to the suspension of OCS therapy in most patients or >50% reduction in the daily OCS dose

Clinical manifestations in patients with PI*MMMalton genotypes. A matter still unsolved in alpha-1 antitrypsin deficiency

We report the genetic variants associated with alpha-1 antitrypsin deficiency (AATD) in 117 patients admitted to our outpatient clinic and characterized by a serum concentration of AAT lower than 113 mg/dL. We focused on the M-like heterozygous variant of the SERPINA1 gene called PI*MMMalton, and describe three patients with this variant. While the role of homozygous AATD in liver and pulmonary disease is well established, the association between heterozygous AATD and chronic liver and pulmonary disease is still under investigation. The PI*MMMalton genotype was found in 5.8% of patients with a pathological genotype of AATD and in 14.3% of the subjects when considering only those with intermediate AATD. There were no liver or renal abnormalities in patients with the PI*MMMalton genotype. The PI*MMMalton patients included here showed a normal liver function, and none had renal function abnormalities or abdominal aortic aneurysm. Only a prevalence of lung disease was detected

The COPD assessment test and the modified Medical Research Council scale are not equivalent when related to the maximal exercise capacity in COPD patients

Introduction: The management and treatment of Chronic Obstructive Pulmonary Disease (COPD) are based on a cutoff point either of ≥ 10 on the COPD Assessment Test (CAT) or of ≥ 2 of the Medical Research Council (mMRC). Up to now, no study has assessed the equivalence between CAT and mMRC, as related to exercise tolerance in COPD. The aim of this study was to investigate as primary outcome the relationship between CAT and mMRC and maximal exercise capacity in COPD patients. We also evaluated as secondary outcome the agreement between CAT (≥ 10) and mMRC (≥ 2) to categorize patients according to their exercise tolerance. Material and methods: 118 consecutive COPD patients (39 females), aged between 47 and 85 years with a wide range of airflow obstruction and lung hyperinflation were studied. Maximal exercise capacity was assessed by cardiopulmonary exercise test. Results: CAT and mMRC scores were significantly related to VO2 peak (p<0.01). CAT (≥ 10) and mMRC (≥ 2) have a high likelihood to be associated to a value of VO2 peak less than 15.7 and 15.6 mL/kg/min, respectively. The interrater agreement between CAT (≥ 10) and mMRC (≥ 2) was found to be fair (κ = 0.20) in all patients but slight when they were subdivided in those with VO2 peak < 15 mL/kg/min and in those with VO2 peak ≥ 15 mL/kg/min (κ = 0.10 and κ = 0.20 respectively). Conclusion: This study shows that CAT and mMRC are useful tools to predict exercise tolerance in COPD, but they cannot be considered as supplementary measures

role of induced sputum in interstitial lung disease

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The impact of monoclonal antibodies on airway smooth muscle contractility in asthma: A systematic review

Airway hyperresponsiveness (AHR) represents a central pathophysiological hallmark of asthma, with airway smooth muscle (ASM) being the effector tissue implicated in the onset of AHR. ASM also exerts pro-inflammatory and immunomodulatory actions, by secreting a wide range of cytokines and chemokines. In asthma pathogenesis, the overexpression of several type 2 inflammatory mediators including IgE, IL-4, IL-5, IL-13, and TSLP has been associated with ASM hyperreactivity, all of which can be targeted by humanized monoclonal antibodies (mAbs). Therefore, the aim of this review was to systematically assess evidence across the literature on mAbs for the treatment of asthma with respect to their impact on the ASM contractile tone. Omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab were found to be effective in modulating the contractility of the ASM and preventing the AHR, but no available studies concerning the impact of reslizumab on the ASM were identified from the literature search. Omalizumab, dupilumab, and tezepelumab can directly modulate the ASM in asthma, by specifically blocking the interaction between IgE, IL-4, and TSLP, and their receptors are located on the surface of ASM cells. Conversely, mepolizumab and benralizumab have prevalently indirect impacts against AHR by targeting eosinophils and other immunomodulatory effector cells promoting inflammatory processes. AHR has been suggested as the main treatable trait towards precision medicine in patients suffering from eosinophilic asthma, therefore, well-designed head-to-head trials are needed to compare the efficacy of those mAbs that directly target ASM contractility specifically against the AHR in severe asthma, namely omalizumab, dupilumab, and tezepelumab

Analisi biomolecolare di ceppi di Canine Distemper Virus (CDV) in furetti domestici (Mustela putorius furo)

L\u2019agente eziologico del cimurro (CDV) appartiene alla famiglia Paramyxoviridae, genere Morbillivirus ed \ue8 causa di una patologia infettiva e contagiosa in canidi, mustelidi e procionidi. Gli Autori, descrivono un caso clinico di cimurro in due furetti domestici vaccinati con un ceppo Onderstepoort avianizzato. e la caratterizzazione biomolecolare del CDV isolato. I furetti presentavano un quadro clinico caratterizzato da dermatite pruriginosa e squamo-purulenta, alla regione del mento, peri-labiale, peri-vulvare ed al condotto uditivo esterno. I soggetti venivano a morte tre settimane dopo l\u2019esordio dei sintomi. I campioni di croste prelevati sono stati sottoposti ad estrazione degli acidi nucleici ed analizzati mediante RT-PCR per CDV. E\u2019 stata effettuata l\u2019analisi con enzimi di restrizione (RFLP-PCR) di conferma, per discriminare i ceppi vaccinali dai ceppi di campo. I prodotti di amplificazione sono stati purificati e sottoposti a sequenziamento. Le sequenze di 1823 nt del gene H del CDV sono state comparate mediante Clustal X con analoghe sequenze di ceppi di campo e ceppi vaccinali disponibili su GeneBank. Sulla base dei dati ottenuti le sequenze sono risultate appartenenti al lineage Europa, ben segregato dal lineage America-1, che raccoglie i principali ceppi vaccinali avianizzati, e differente dal cluster dei ceppi Rockborn-like. Il sequenziamento ha confermato il risultato ottenuto con la RFLP-PCR e la mancanza di relazione con il ceppo vaccinale inoculato. Le due sequenze ottenute, presentando un\u2019omologia nucleotidica elevata per ceppi isolati da cani in Italia, sono risultate differenti dal lineage Wildlife. Nel furetto l\u2019infezione da cimurro ha un esito fatale quasi nel 100% dei casi e viene controllata attraverso l\u2019uso di vaccini. Questo lavoro rappresenta un contributo alla esigua disponibilit\ue0 bibliografica in merito alle infezioni da CDV nei mustelidi ed implementa i dati disponibili sui ceppi virali circolanti. Il metodo diagnostico descritto rappresenta un sistema rapido e sensibile per la diagnosi dell\u2019infezione da cimurro

Clinical manifestations of a new alpha-1 antitrypsin genetic variant: Q0parma

Alpha-1 antitrypsin deficiency is an autosomal, codominant disorder caused by mutations of the SERPINA1 gene. Several mutations of SERPINA1 have been described associated with the development of pulmonary emphysema and/or chronic liver disease and cirrhosis. Here, we report a very rare PI*Q0parma variant identified for the first time in an Italian family originally from the city of Parma in Northern Italy