Clinical Characterization and Predictive Factors for Progression in a Cohort of Patients with Interstitial Lung Disease and Features of Autoimmunity: The Need for a Revision of IPAF Classification Criteria.

Background and Objectives: The "interstitial pneumonia with autoimmune features" (IPAF) criteria have been criticized because of the exclusion of usual interstitial pneumonia (UIP) patients with a single clinical or serological feature. To classify these patients, the term UIPAF was proposed. This study aims to describe clinical characteristics and predictive factors for progression of a cohort of interstitial lung disease (ILD) patients with at least one feature of autoimmunity, applying criteria for IPAF, specific connective tissue diseases (CTD), and a definition of UIPAF when possible. Methods: We retrospectively evaluated data on 133 consecutive patients with ILD at onset associated with at least one feature of autoimmunity, referred by pulmonologists to rheumatologists from March 2009 to March 2020. Patients received 33 (16.5-69.5) months of follow-up. Results: Among the 101 ILD patients included, 37 were diagnosed with IPAF, 53 with ILD-onset CTD, and 11 with UIPAF. IPAF patients had a lower prevalence of UIP pattern compared to CTD-ILD and UIPAF patients (10.8% vs. 32.1% vs. 100%, p < 0.01). During the follow-up, 4 IPAF (10.8%) and 2 UIPAF (18.2%) patients evolved into CTD-ILD. IPAF patients presented features not included in IPAF criteria, such as sicca syndrome (8.1%), and were more frequently affected by systemic hypertension (p < 0.01). Over one year, ILD progression (greater extent of fibrosis on HRCT and/or decline in PFTs) was less frequent in the IPAF group compared to CTD-ILD and UIPAF (32.3% vs. 58.8% vs. 72.7, p = 0.02). A UIP pattern and an IPAF predicted a faster (OR: 3.80, p = 0.01) and a slower (OR: 0.28, p = 0.02) ILD progression, respectively. Conclusions: IPAF criteria help identify patients who might develop a CTD-ILD, even though a single clinical or serological feature is respected. Future revisions of IPAF criteria should include sicca syndrome and separate UIP-pattern into a different definition (UIPAF), given its association with a different prognosis, independently from ILD classification.

Opening of a respiratory intermediate care unit in a general hospital: impact on mortality and other outcomes.

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.

Nintedanib in Idiopathic Pulmonary Fibrosis: Tolerability and Safety in a Real Life Experience in a Single Centre in Patients also Treated with Oral Anticoagulant Therapy.

Idiopathic pulmonary fibrosis (IPF) is a rare and severe disease with a median survival of ~3 years. Nintedanib (NTD) has been shown to be useful in controlling interstitial lung disease (ILD) in IPF. Here we describe the experience of NTD use in IPF in a real-life setting. Objective. Our objective was to examine the safety profile and efficacy of nintedanib even in subjects treated with anticoagulants. Clinical data of patients with IPF treated with NTD at our center were retrospectively evaluated at baseline and at 6 and 12 months after the introduction of NTD. The following parameters were recorded: IPF clinical features, NTD tolerability, and pulmonary function tests (PFT) (i.e., Forced Vital Capacity (FVC) and carbon monoxide diffusing capacity (DLCO)). In total, 56 IPF patients (34% female and 66% male, mean onset age: 71 ± 11 years, mean age at baseline: 74 ± 9 years) treated with NTD were identified. At enrollment, HRCT showed an UIP pattern in 45 (80%) and a NSIP in 11 (20%) patients. For FVC and FEV1 we found no significant change between baseline and 6 months, but for DLCO we observed a decrease (p = 0.012). We identified a significant variation between baseline and 12 months for FEV1 (p = 0.039) and for DLCO (p = 0.018). No significant variation was observed for FVC. In the cohort, 18 (32%) individuals suspended NTD and 10 (18%) reduced the dosage. Among individuals that suspended the dosage, 14 (78%) had gastrointestinal (GI) collateral effects (i.e., diarrhea being the most common complaint (67%), followed by nausea/vomiting (17%) and weight loss (6%). Bleeding episodes have also not been reported in patients taking anticoagulant therapy. (61%). One patient died within the first 6 months and two subjects died within the first 12 months. In a real-life clinical scenario, NTD may stabilize the FVC values in IPF patients. However, GI side effects are frequent and NTD dose adjustment may be necessary to retain the drug in IPF patients. This study confirms the safety of NTD, even in patients treated with anticoagulant drugs.

Pulmonary Sarcoidosis and Immune Dysregulation: A Pilot Study on Possible Correlation.

BACKGROUND: Sarcoidosis is a systemic inflammatory disease characterized by an altered inflammatory response. OBJECTIVE: The aim of this study was to evaluate whether immune system alterations detected by lymphocyte typing in peripheral blood correlate with the severity of sarcoidosis, calculated according to two separate severity scores proposed by Wasfi in 2006 and Hamzeh in 2010. MATERIALS AND METHODS: Eighty-one patients were recruited, and clinical data and laboratory tests at the time of diagnosis were obtained in order to assess the severity index score and investigate any statistically significant correlation with the cytofluorimetry data. RESULTS: Our data demonstrated that none of the two scores show an association with the level of total lymphocytes or lymphocyte subclasses. LIMITATIONS: First of all, the sample taken into consideration is small. The assessment was performed only at disease onset and not during the disease. Furthermore, the severity scores do not take into account disease activity (measured by PET/CT or gallium scintigraphy). CONCLUSIONS: Lymphocyte subpopulation values at the time of diagnosis do not appear to correlate with disease severity at onset.

Cytokine Profiles as Potential Prognostic and Therapeutic Markers in SARS-CoV-2-Induced ARDS.

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.

Interstitial lung disease in patients with antisynthetase syndrome: a retrospective case series study.

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.

Respiratory muscle training with enzyme replacement therapy improves muscle strength in late - onset Pompe disease.

BACKGROUND: Pompe disease is an autosomal recessive metabolic disorder caused by the deficiency of the lysosomal enzyme acid α-glucosidase. This deficiency leads to glycogen accumulation in the lysosomes of muscle tissue causing progressive muscular weakness particularly of the respiratory system. Enzyme replacement therapy (ERT) has demonstrated efficacy in slowing down disease progression in infants. Despite the large number of studies describing the effects of physical training in juvenile and adult late onset Pompe disease (LOPD). There are very few reports that analyze the benefits of respiratory muscle rehabilitation or training. METHODS: The effectiveness of respiratory muscle training was investigated using a specific appliance with adjustable resistance (Threshold). The primary endpoint was effect on respiratory muscular strength by measurements of MIP and MEP. Eight late-onset Pompe patients (aged 13 to 58 years; 4 female, 4 male) with respiratory muscle deficiency on functional respiratory tests were studied. All patients received ERT at the dosage of 20 mg/kg/every 2 weeks and underwent training with Threshold at specified pressures for 24 months. RESULTS: A significant increase in MIP was observed during the follow-up of 24 month: 39.6 cm H2O (+ 25.0%) at month 3; 39.5 cm H2O (+ 24.9%) at month 6; 39.1 cm H2O (+ 23.7%) at month 9; 37.3 cm H2O (+ 18.2%) at month 12; and 37.3 cm H2O (+ 17.8%) at month 24. Median MEP values also showed a significant increase during the first 9 months: 29.8 cm H2O, (+ 14.3%) at month 3; 31.0 cm H2O (+ 18.6) at month 6; and 29.5 cm H2O (+ 12.9) at month 9. MEP was then shown to be decreased at months 12 and 24; median MEP was 27.2 cm H2O (+ 4.3%) at 12 months and 26.6 cm H2O (+ 1.9%) at 24 months. The FVC remain stable throughout the study. CONCLUSION: An increase in respiratory muscular strength was demonstrated with Threshold training when used in combination with ERT.

Inspiratory muscle training for diaphragm dysfunction after cardiac surgery.

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.

Methylprednisolone infusion for life-threatening H1N1-virus infection.

BACKGROUND: During winter 2009 we treated with prolonged corticosteroid infusion eight consecutive patients affected by H1N1-virus infection and severe pneumonia. The most severe patient was a previously healthy 30-year-old man admitted to hospital because of bilateral pneumonia and severe acute respiratory failure. METHOD: H1N1-virus infection was detected by broncho-alveolar lavage performed on day 1. After some days following admission the patient was still in a life-threatening state, not responding to oseltamivir, protective mechanical ventilation and veno-arterial extracorporeal membrane oxygenation (ECMO). RESULTS: The addition of methylprednisolone infusion at a stress dose (1 mg/kg/24 h) as rescue therapy significantly and rapidly improved the clinical condition. Weaning from ECMO and invasive mechanical ventilation was possible within a relatively few days. CONCLUSION: According to the literature reports more than 34% of H1N1-virus severe infections were treated with corticosteroids. This report and our experience may suggest a possible life-saving use of corticosteroids at a stress dose in severely ill patients with an H1N1-virus infection that is not responding to the most advanced treatments.