A Real-Life Multicenter National Study on Nintedanib in Severe Idiopathic Pulmonary Fibrosis.

BACKGROUND: Two therapeutic options are currently available for patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF): pirfenidone and nintedanib. To date, there is still insufficient data on the efficacy of these 2 agents in patients with more severe disease. OBJECTIVES: This national, multicenter, retrospective real-life study was intended to determine the impact of nintedanib on the treatment of patients with severe IPF. METHODS: All patients included had severe IPF and had to have at least 6 months of follow-up before and at least 6 months of follow-up after starting nintedanib. The aim of the study was to compare the decline in lung function before and after treatment. Patient survival after 6 months of therapy with nintedanib was assessed. RESULTS: Forty-one patients with a forced vital capacity (FVC) ≤50% and/or a diffusing capacity of the lung for carbon monoxide (DLCO) ≤35% predicted at the start of nintedanib treatment were enrolled. At the 6-month follow-up, the decline of DLCO (both absolute and % predicted) was significantly reduced compared to the pretreatment period (absolute DLCO at the -6-month, T0, and +6-month time points (5.48, 4.50, and 5.03 mmol/min/kPa, respectively, p = 0.03; DLCO% predicted was 32.73, 26.54, and 29.23%, respectively, p = 0.04). No significant beneficial effect was observed in the other functional parameters analyzed. The 1-year survival in this population was 79%, calculated from month 6 of therapy with nintedanib. CONCLUSIONS: This nationwide multicenter experience in patients with severe IPF shows that nintedanib slows down the rate of decline of absolute and % predicted DLCO but does not have significant impact on FVC or other lung parameters.

Clinical and Serological Characteristics of a Monocentric Cohort of Patients Affected by Interstitial Pneumonia with Autoimmune Features (IPAF).

Introduction: Interstitial lung diseases (ILDs) are diseases characterised by excessive deposition of collagen matrices in the pulmonary interstitium. Some of them are considered idiopathic (idiopathic pulmonary fibrosis - IPF), others are related to known pathologies such as connective tissue diseases (CTDs-ILD). Patient affected by ILD and features referable to CTD, not satisfying CTD criteria, are called Interstitial pneumonia with autoimmune features (IPAF) patients. Objective: The aim of this report was to investigate clinical and serologic features of a monocentric cohort of patients with IPAF. Another objective was to describe the autoantibody profile, clinical features, High Resolution Computerised Tomography (HRCT) and Nailfold Video Capillaroscopy (NVC) patterns. Methods: 36 IPAF patients were consecutively enrolled. Clinical, serological, and morphological features were collected. Results: 36 consecutive IPAF patients were enrolled from January 2021 to January 2022. Raynaud's phenomenon was the most frequent symptom identified. We also described other signs and symptoms not included in IPAF criteria. 36,1% of patients demonstrated a Usual Interstitial Pneumonia (UIP) pattern by HRCT. Pulmonary arterial pressure estimation (PAPs) resulted elevated (≥ 25 mmHg) in 6 patients. Antinuclear antibodies (ANA) ≥ 1/80 was the most frequent autoantibody, followed by anti-Ro, in patients with UIP pattern and Non-Specific Interstitial Pneumonia (NSIP) pattern at HRCT. NVC highlighted non-specific microangiopathy as the most common pattern especially in UIP patients. Conclusions: This paper may contribute to stimulate the interest in better characterisation of clinical, serologic, and instrumental features for IPAF patients by redefining IPAF classification criteria in order to treat them as best as possible.

Self-reported compliance with drug therapy during the first SARS-CoV-2 Italian lockdown in patients with respiratory disease.

BACKGROUND: Low compliance with drug therapy in patients with chronic respiratory diseases was a well-known issue even before the coronavirus pandemic, but its causes are not yet fully defined. OBJECTIVE: To verify the adherence to drug therapy in patients with respiratory disease during the COVID-19 pandemic. METHODS: From June to September 2020, about 700 patients of the Forlanini Hospital who had been unmonitored during the March-May 2020 lockdown in Italy received a questionnaire during the pneumological check-up based on self-reported information on compliance with therapy during lockdown. RESULTS: 284 out of the 418 returned questionnaires could be used in this study: 179 patients (63.0%) responded positively to the continuation of therapy, 18 (6.3%) reduced the dosage of their medication and 82 (28.9%) interrupted the therapy. CONCLUSIONS: The low percentage of patients that reduced their drug dosage may be due to an increased awareness of drug treatment benefits, and may also be ascribed to the Government healthcare strategy during lockdown.

Road Toward a New Model of Care for Idiopathic Pulmonary Fibrosis in the Lazio Region.

A timely, confirmed diagnosis of Idiopathic Pulmonary Fibrosis (IPF) has a significant impact on the evolution of the disease. The current model of care in the Lazio region (in Italy) was assessed on the basis of real-world data provided by the four reference centers responsible for diagnosing and treating IPF. The 5-year, population-based, retrospective longitudinal study provided the data that is at the basis of the current proposal for a new clinical and therapeutic pathway (DTCP) and has been shared with regional decision makers. A DTCP must be defined and based on four pillars: GPs, pulmonologists, IPF centers, and telemedicine. Each must play a role within a sort of hub-and-spoke model. IPF centers remain the hubs, while spokes are identified in trained GPs and pulmonologists.

Raising awareness on physician-patient communication in IPF: an Italian multicenter study exploring the pulmonologist's perspective.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) remains a debilitating, poor prognosis disease requiring a patient-centered approach. OBJECTIVES: To explore the pulmonologist's perspective on physician-patient communication. METHODS: A faculty of psychologists and pulmonologists organized a training course consisting of two workshops 12 months apart. Self-assessment questionnaires (pre- and post-course), role play (RP) simulations (during both workshops) and clinical consultation observations followed by semi-structured interviews (during the 12 months) were employed to evaluate the pulmonologists' knowledge of patient-centered medicine and communication/relational skills (questionnaires), their communication style (RP) and possible communication/relational difficulties (semi-structured interviews). RESULTS: Twenty-three pulmonologists attended the first workshop and 14 the second one; 10 attended both. The questionnaires revealed the interest in patient-centered medicine and communication but also the need for deeper knowledge and improved skills. From the RP sessions performed during the first workshop, a disease-oriented approach emerged; notably, after the training, some improvements suggested a more patient-centered approach, e.g., a more frequent exploration of the patient agenda. Finally, the semi-structured interviews allowed to identify the low patients' cultural level and the poor general knowledge of IPF among the barriers hampering an effective communication with the clinician, who, however, is responsible for overcoming these obstacles. CONCLUSIONS: Despite the overall disease-prone approach to IPF patients, there was room for improvement through adequate training, which, in practice, may ameliorate communication and drive towards patient-centeredness. Exploring the pulmonologists' needs may help tailoring training interventions. Raising awareness on these topics is crucial to ensure IPF patients optimal care.

Mechanical ventilation in patients with end-stage idiopathic pulmonary fibrosis.

BACKGROUND: Acute respiratory failure (ARF) occurring during idiopathic pulmonary fibrosis (IPF) is associated with a poor prognosis. In this subset of individuals, mechanical ventilation (MV) may be required. OBJECTIVES: We analysed the characteristics of a group of IPF patients undergoing MV for ARF in order to give some indications on the supposed prognosis. METHODS: Hospital records of 34 consecutive patients with IPF, who underwent MV for ARF, were retrospectively examined. Demographic data, time from diagnosis, gas exchange, Acute Physiology and Chronic Health Evaluation (APACHE) II score, ARF causes and MV failure were recorded. RESULTS: Fifteen subjects (group A) underwent invasive MV and 19 patients (group B) non-invasive ventilation (NIV). The 2 groups were different for disease severity (APACHE II score 24.2 +/- 6 vs. 19.5 +/- 5.9; p = 0.01). Both ventilatory strategies temporarily increased PaO2/FiO2 as compared with spontaneous breathing (group A: 148.5 +/- 52 vs. 99 +/- 39, p = 0.0004; group B: 134 +/- 36 vs. 89 +/- 26, p = 0.0004). NIV reduced the respiratory rate (26 +/- 7 vs. 36 +/- 9 with spontaneous breathing; p = 0.002). Duration of MV correlated with the time of evolution of IPF (r = 0.45; p = 0.018). The in-hospital mortality rate was 85% (100% for invasive MV, 74% for NIV). Four of the 5 survivors died within 6 months from hospital discharge (range 2-6 months). CONCLUSIONS: MV does not appear to have a significant impact on the survival of patients with end-stage IPF. NIV may be useful for compassionate use, providing relief from dyspnoea and avoiding aggressive approaches.

Rituximab in Antimelanoma Differentiation-Associated Protein-5 Dermatomyositis with Interstitial Lung Disease.

In this paper, we report a challenging case of a middle-age woman who developed antimelanoma differentiation-associated protein-5 dermatomyositis (anti-MDA5 DM) with interstitial lung disease (ILD) and was successfully treated with rituximab (RTX), after failure of a first-line therapy.

Nutrition in Patients with Idiopathic Pulmonary Fibrosis: Critical Issues Analysis and Future Research Directions.

In idiopathic pulmonary fibrosis (IPF), several factors may have a negative impact on the nutritional status, including an increased respiratory muscles load, release of inflammation mediators, the coexistence of hypoxemia, and physical inactivity. Nutritional abnormalities also have an impact on IPF clinical outcomes. Given the relevance of nutritional status in IPF patients, we sought to focus on some critical issues, highlighting what is known and what should be further learned about these issues. We revised scientific literature published between 1995 and August 2019 by searching on Medline/PubMed and EMBASE databases including observational and interventional studies. We conducted a narrative review on nutritional assessment in IPF, underlining the importance of nutritional evaluation not only in the diagnostic process, but also during follow-up. We also highlighted the need to keep a high level of attention on cardiovascular comorbidities. We also focused on current clinical treatment in IPF with Nintedanib and Pirfenidone and management of gastrointestinal adverse events, such as diarrhea, induced by these antifibrotic drugs. Finally, we concentrated on the importance of pulmonary rehabilitation program, including nutritional assessment, education and behavioral change, and psychological support among its essential components. More attention should be devoted to the assessment of the undernutrition and overnutrition, as well as of muscle strength and physical performance in IPF patients, taking also into account that an adequate clinical management of gastrointestinal complications makes IPF drug treatments more feasible.

Pirfenidone in real life: A retrospective observational multicentre study in Italian patients with idiopathic pulmonary fibrosis.

RATIONALE: Real-world data on pirfenidone treatment of patients with idiopathic pulmonary fibrosis (IPF) are limited. This study assessed the effectiveness of pirfenidone in a large real-life Italian IPF cohort. METHODS: IRENE was an observational, retrospective study of patients with IPF treated with pirfenidone in routine clinical practice (18 centres). At Month 6, a mandatory re-evaluation of forced vital capacity (FVC) decline (absolute change < 10%) was required to continue pirfenidone. The primary effectiveness outcomes were absolute change from baseline in FVC and the percentage of patients with ≥ 10% absolute decline in % predicted FVC at Month 12. Safety was described by adverse event (AE) occurrence. Prespecified subgroups included sex, age, presence/absence of emphysema, usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography, and baseline lung function. RESULTS: The study included 379 patients (mean age, 67.6 years; 78.1% male). Mean change from baseline in FVC and the percentage of patients with ≥ 10% absolute decline in % predicted FVC at Month 12 were -81.8 mL (SD, 419.6 mL; P = 0.002) and 16.0% (95% CI, 12.2-20.9%), respectively. Disease progression was similar across prespecified subgroups, including patients with definite vs possible UIP. Overall, 211 AEs occurred in 149 patients (39.3%), with serious AEs in 31 patients (8.2%) and 9 discontinuations due to AEs. Skin and gastrointestinal AEs were most frequent. Fifteen patients (4.0%) died. CONCLUSIONS: The decline in FVC and the safety profile observed in this real-world IPF cohort were consistent with the findings of the Phase III pirfenidone trials.

The prognostic role of Gender-Age-Physiology system in idiopathic pulmonary fibrosis patients treated with pirfenidone.

INTRODUCTION: Gender, age, physiology (GAP) system have proven to be an easy tool for predicting disease stages and survival in idiopathic pulmonary fibrosis (IPF) patients. OBJECTIVE: To validate mortality risk as determined by the GAP system in a real-life multicentre IPF population treated with pirfenidone. METHODS: The study included patients who received pirfenidone for at least 6 months. The GAP calculator and the GAP index were determined. The primary outcome was all-cause mortality. The prognostic accuracy of the GAP system was evaluated with respect to calibration and discrimination. RESULTS AND CONCLUSION: Sixty-eight IPF patients were enrolled in the study. The median follow-up was 2.4 years (range 0.1-7.4 years). A total of 22 deaths as first event (32%) and of 10 lung transplantation (15%) were recorded. The cumulative incidence of mortality at 1, 2 and 3 years was 10.4%, 22.4% and 38.4%, respectively. The differences between the predicted and observed mortality were not significant for the GAP index while the observed mortality become comparable to that predicted by the GAP calculator only in the third year of follow-up. The C-index for the GAP index was 0.74 (95% CI 0.57-0.93) while the C-statistic value for the GAP calculator was 0.77 (95% CI 0.59-0.95).

COPD: maximization of bronchodilation.

The most recent guidelines define COPD in a multidimensional way, nevertheless the diagnosis is still linked to the limitation of airflow, usually measured by the reduction in the FEV1/FVC ratio below 70%. However, the severity of obstruction is not directly correlated to symptoms or to invalidity determined by COPD. Thus, besides respiratory function, COPD should be evaluated based on symptoms, frequency and severity of exacerbations, patient's functional status and health related quality of life (HRQoL). Therapy is mainly aimed at increasing exercise tolerance and reducing dyspnea, with improvement of daily activities and HRQoL. This can be accomplished by a drug-induced reduction of pulmonary hyperinflation and exacerbations frequency and severity. All guidelines recommend bronchodilators as baseline therapy for all stages of COPD, and long-acting inhaled bronchodilators, both beta-2 agonist (LABA) and antimuscarinic (LAMA) drugs, are the most effective in regular treatment in the clinically stable phase. The effectiveness of bronchodilators should be evaluated in terms of functional (relief of bronchial obstruction and pulmonary hyperinflation), symptomatic (exercise tolerance and HRQoL), and clinical improvement (reduction in number or severity of exacerbations), while the absence of a spirometric response is not a reason for interrupting treatment, if there is subjective improvement in symptoms. Because LABA and LAMA act via different mechanisms of action, when administered in combination they can exert additional effects, thus optimizing (i.e. maximizing) sustained bronchodilation in COPD patients with severe airflow limitation, who cannot benefit (or can get only partial benefit) by therapy with a single bronchodilator. Recently, a fixed combination of ultra LABA/LAMA (indacaterol/glycopyrronium) has shown that it is possible to get a stable and persistent bronchodilation, which can help in avoiding undesirable fluctuations of bronchial calibre.