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Background. Glucocorticoids (GCs) have been shown to reduce mortality and the need for invasive mechanical ventilation (IMV) in SARS-CoV-2-induced acute respiratory distress syndrome (ARDS). It has been suggested that serum cytokines levels are markers of disease severity in ARDS, although there is only limited evidence of a relationship between the longitudinal cytokine profile and clinical outcomes in patients with SARS-CoV-2-induced ARDS treated with GC. Methods. We conducted a single-center observational study to investigate serial plasma cytokine levels in 17 patients supported with non-invasive ventilation (NIV) in order to compare the response in five patients who progressed to IMV versus 12 patients who continued with NIV alone. All patients received methylprednisolone 80 mg/day continuous infusion until clinical improvement. Results. The study groups were comparable at baseline. All patients survived. Although IL-6 was higher in the NIV group at baseline, several cytokines were significantly higher in the IMV group on day 7 (IL-6, IL-8, IL-9, G-CSF, IP-10, MCP-1, MIP-1α) and 14 (IL-6, IL-8, IL-17, G-CSF, MIP-1α, RANTES). No significant differences were observed between groups on day 28. Conclusions. Patients in the IMV group had higher inflammation levels at intubation than the NIV group, which may indicate a higher resistance to glucocorticoids. Higher GC doses or a longer treatment duration in these patients might have allowed for a better control of inflammation and a better outcome. Further studies are required to define the prognostic value of cytokine patterns, in terms of both GC treatment tailoring and timely initiation of IMV.

Purpose Antisynthetase syndrome (ASS) is a rare systemic autoimmune condition associated to the presence of anti-aminoacyl-tRNA synthetase antibodies. Interstitial lung disease (ILD) is the most prevalent manifestation of ASS and is a major determinant of morbidity and mortality. The aim of this study was to describe the radiological characteristics of patients with ASS-associated-ILD in our institution. Materials and methods Medical records from 2014 to 2020 were retrospectively reviewed and patients with a diagnosis of ASS and evidence of ILD on HRCT were included. HRCT images were reviewed by two thoracic radiologists in consensus. Five HRCT patterns were defined: cellular non-specific interstitial pneumonia (NSIP), organizing pneumonia (OP), mixed NSIP/OP pattern, acute interstitial pneumonia (AIP) pattern and fibrotic pattern. Descriptive statistics was calculated for all variables. Results Twenty-two patients with ASS who met inclusion criteria were included. The disease presented with the typical triad of ASS in 45% of patients, 55% had ILD only at the onset. Cellular NSIP was present in 27% of patients, OP in 23%, mixed NSIP/OP in 9%, AIP in 18% and a fibrotic pattern in 23%. Conclusion HRCT findings in ASS-associated ILD are often non-specific; nevertheless, it is important to consider this diagnosis, especially in patients presenting with acute onset of symptoms.

Background:Interstitial lung disease (ILD) can be the first manifestation of connective tissue disease (CTD) and rheumatoid arthritis (RA). Pulmonologists are usually the first referral in these patients.Objectives:To determine: 1) the prevalence of ILD as initial manifestation of CTD or RA 2) clinical characteristics of such patients.Methods:From a database of consecutive patients with CTD or RA referred to our academic hospital from 2009 and 2017, we selected all the patients with ILD as initial manifestation of the disease. Periodic multidisciplinary evaluations were performed during a median follow-up of 48 (35-50) months.Results:1) Fifty-four of the 427 patients with CTD or RA (12.6%) had ILD as initial manifestation (mean age: 63.9±12.9 yrs, F/M ratio: 20/34). Autoimmune myositis was diagnosed in 16/54 patients (29.6%), systemic sclerosis in 11 patients (20.4%), RA in 9 patients (16.7%), Sjogren syndrome in 9 patients (16.7%) and SLE in 3 patients (5.5%). Six patients remained classified as IPAF (11.1%). Among the Rheumatology patients we followed-up in the same period, autoimmune myositis had the highest prevalence of ILD as initial manifestation (63.6%), followed by Sjogren syndrome (20.5%), systemic sclerosis (20.0%), RA (3.4%), and SLE (3.3%). 2) Patients with initial ILD were all firstly evaluated by the Pulmonologist and the main reasons for Rheumatology referral were positivity for one or more autoantibodies (57.4%), mainly ANA≥1:320, and joint pain (29.6%). Thirty-six patients (66.7%) received steroid and/or immunosuppressive therapy in the six months before the first Rheumatology visit to relieve respiratory symptoms. Twenty of these patients (58.8%) had rheumatic manifestations during steroid tapering. ILD CT patterns were NSIP (25 patients, 52.1%), UIP (18 patients, 33.4%), and organizing pneumonia (5 patients, 9.3%). In four patients (4.5%), autoantibodies became positive during the follow-up. The final diagnosis of CTD- or RA-ILD was made after a median period of 16.5 (6-39) months from the clinical onset. At the time of diagnosis, average FVC was 90.4±18.7% of predicted, DLCO 55.4±20.2% and the median GAP index was 3 (2-3). During the median follow-up of 48 months, eight patients (14.8%) had a decline in DLCO of ≥ 15% predicted and/or a decline in FVC of ≥ 10% despite immunosuppressive drugs. Nine patients (17%) died and six of these patients (11.1%) for causes related to ILD.Conclusion:In our study population, the prevalence of ILD as initial manifestation of CTD or RA was 12.6%. Autoimmune myositis, systemic sclerosis and Sjogren syndrome were the most frequent diagnosis. As our data confirmed, ILD is a major cause of death in patients with systemic autoimmune diseases and can progress despite immunosuppression [1]. Furthermore, clinical features may become evident even months after the disease onset. A multidisciplinary evaluation is therefore essential, not only at the time of diagnosis but also during the follow-up [2].References:[1] A. Fischeret al.Progressive fibrosing interstitial lung disease associated with systemic autoimmune diseases.Clin Rheum(2019); 38:2673-81[2] F. Furini,et al. The role of the Multidisciplinary Evaluation of Interstitial Lung Diseases: Systematic Literature Review of the Current Evidence and Future Perspectives.Front Med(2019); 6:246Disclosure of Interests:None declared

OBJECTIVE: Diaphragm dysfunction is a complication of cardiac surgery with partial or absent spontaneous recovery in most cases. Surgical diaphragm plication represents the only option when symptoms persist. Because training improves functional nerve recovery after a nerve lesion, we hypothesized that early diaphragm muscle training may be beneficial. METHODS: A prospective, randomized at 2:1 ratio, controlled trial of diaphragm training using an adjustable pressure device (Threshold; Philips Respironics Inc, Murrysville, Pa) versus no training (sham device) was performed in patients with diaphragm paralysis after major cardiac surgery. This 1-year study recruited consecutive adult patients with sniff fluoroscopy-defined diaphragm paralysis after coronary bypass, valve replacement, or both. The outcome measures were diaphragm function recovery assessed by sniff fluoroscopy, maximum inspiratory and expiratory pressures, and lung function tests. RESULTS: A total of 69 patients were randomized. At 12 months, 52 patients completed the study assessments, 36 in the treatment group and 16 in the control group. Inspiratory muscle training produced a significant improvement of diaphragm mobility after 12 months (P < .001). Most patients in the training group (77.78%) experienced a partial improvement (41.67%) or achieved a complete improvement (36.11%) versus no improvement (87.5%) or partial recovery (12.5%) among controls. CONCLUSIONS: Inspiratory muscle training may improve inspiratory muscle strength and increases paralyzed diaphragm mobility.

Background: Respiratory intermediate care units (RICUs) are specialized areas aimed at optimizing the cost-benefit ratio of care. No data exist about the impact of opening a RICU on hospital outcomes. Objectives: We wondered if opening a RICU may improve the outcomes of patients with acute respiratory failure (ARF), acute exacerbation of chronic obstructive pulmonary disease (AECOPD), or community-acquired pneumonia (CAP). Methods: We analyzed the discharge abstracts of 2,372 admissions to the RICU and internal medicine units (IMUs) for ARF, AECOPD, and CAP. The IMUs at the Hospital of Trieste comprise emergency and internal wards. In order to investigate the determinants of outcomes, a matched case-control study was performed using clinical records. Results: The in-hospital mortality rate was lower in the RICU vs. IMUs (5.4 vs. 19.1%, p = 0.0001). Statistical differences did not change when comparing the RICU with the emergency and internal wards. After adjusting for potential confounders, the risk of death for patients with CAP, AECOPD, or ARF was significantly higher in the IMUs than in the RICU (OR 6.90, 3.19, and 6.7, respectively, p < 0.04). Both the frequency of transfer to the ICU (6 vs. 12%, p = 0.0001, OR 0.38) and the hospital stay (9.3 vs. 12.1 days, p = 0.0001) were reduced in patients admitted to the RICU compared to those admitted to non-RICUs. Significant differences were found in care management concerning chest physiotherapy, mechanical ventilation, antibiotics, and corticosteroids. Conclusions: The opening of a RICU may be advantageous to reduce in-hospital mortality, the need for ICU admission, and the hospital stay of patients with AECOPD, CAP, and ARF. Better use of care resources contributed to better patient management in the RICU.

In spite of evidence-based consensus recommendations on exercise training for patients with pulmonary arterial hypertension (PAH) its use outside specialized rehabilitation Centers has been accounted a handful of reports. Dyspnoea and fatigue are common symptoms reducing the exercise tolerance of subjects with PAH even when specific drug are correctly administered. Moreover, the mechanisms of exercise limitation in subjects with PAH are known and thandful of reports. There is evidence of impaired signaling between the periphery and central hemodynamic performance. Exercise training has recently been proven to be effective and safe to enhance physical performance in patients with PAH already treated with specific drug therapy. The rationale of training in PAH has been specifically proven also in experimental animal models of PAH. Moreover, repeated positive results in randomized controlled trials and observational studies in humans gave convincing evidence on the beneficial effects of exercise training as a routine treatment for patients with PAH. To date only 3 small randomized controlled trials and several non-randomized experiences were published in the last decade. Nevertheless, there is a full concordance among all studies, unrespective of the design, training protocol and any possible bias. Exercise training showed to improve physical performance and daily activity, reducing dyspnoea and fatigue, and enhancing the quality of life and muscle strength. So, the final message from the available literature reports is a strong recommendation to adopt exercise training and cardiopulmonary rehabilitation programs for any patient suffering from exertional dyspnoea and fatigue. Many questions remain unanswered regarding the optimization of the exercise training and rehabilitation programs. Ongoing rehabilitative trials in patients with PAH will help answer some of the remaining questions.

The global spread of multidrug-resistant strains of tuberculosis (TB) mycobacteria was one of the main reasons leading the World Health Organisation to launch the Stop TB program worldwide. In spite of a slow decline of TB incidence and mortality worldwide, multidrug-resistant TB (MDR-TB) has increased in several countries. MDR-TB is caused by organisms that are resistant to at least isoniazid and rifampicin. The most drug-resistant forms of TB are the extensively drug-resistant TB (XDR-TB) strains caused by organisms that are resistant also to fluoroquinolones and any of the second-line anti-TB injectable drugs. XDR-TB can take 2 years or more to treat with drugs that are less effective, more toxic, and more expensive. Mortality for XDR-TB is very high, and the risk of the transmission between persons of XDR-TB strains is a matter of concern for health systems. Major issues associated with enhanced XDR-TB are non-implementation of DOT (directly observed therapy) and DOT expansion strategies, the insufficient supply or the poor quality of the anti-tuberculosis drugs, and the inadequate intake of the anti-tuberculosis medicines. Nevertheless, prior treatment of MDR-TB with second-line drugs is the strongest associated factor increasing the risk for XDR tuberculosis more than fourfold. Specialized rapid, effective diagnostic methods, including drug-sensitivity testing, are essential for a precise diagnosis of XDR-TB, and subsequent proper treatment. The global rise and spread of XDR-TB have serious effects on TB-control programs, and urge effective health policy responses. National TB control programmes working with all health services can prevent XDR-TB by ensuring that all the physicians and professionals caring for people with TB adhere to the International Standards for TB Care. Specialized centres at regional and national levels should be dedicated to care for difficult-to-treat and untreatable patients with XDR-TB.

The use of corticosteroids in the management of pneumonia is still a controversial issue. The physicians in daily clinical practice often use corticosteroids in patients with pneumonia for different reasons all over the world. As an example of real life is the frequent use of corticosteroids to treat patients with pneumonia due to H1N1 pandemic influenza in spite of WHO’ statements that clearly discouraged this therapy. In fact, the literature up to august 2012 reported a total of 6,650 patients with pneumonia due to H1N1 virus infection (of whom 2,515 were ICU patients): corticosteroids were used with various dose regimen in 2404 patients (37.8%). The attitude of international guidelines on pneumonia in using steroids do not help the clinician to clearly choice when and how to treat pneumonia with steroids. However, stress doses of corticosteroids are suggested by some major guidelines on community-acquired pneumonia in case of severe episodes with sepsis. To date, there are 10 randomised controlled trials assessing the effectiveness of corticosteroids for community-acquired pneumonia globally involving 1090 participants . Most of the trials adopted stress doses of glucorticoids for 4-7 days. The evidence from these trials taken separately is weak due to limitations of the studies themselves, but a Cochrane review and a systematic review found benefit using prolonged low doses of glucocorticoids in severe community-acquired pneumonia. Moreover, such a strategy decreases vasopressor dependency and appears to be safe. Nevertheless, larger trials with more patients and clinically important end-points were claimed to provide robust evidence. Finally, infection surveillance is critical in patients treated with corticosteroids, and to prevent the rebound phenomenon, the drug should be weaned slowly.