Symptomatic post COVID patients have impaired alveolar capillary membrane function and high VE/VCO2.

BACKGROUND: Post COVID-19 syndrome is characterized by several cardiorespiratory symptoms but the origin of patients' reported symptomatology is still unclear. METHODS: Consecutive post COVID-19 patients were included. Patients underwent full clinical evaluation, symptoms dedicated questionnaires, blood tests, echocardiography, thoracic computer tomography (CT), spirometry including alveolar capillary membrane diffusion (DM) and capillary volume (Vcap) assessment by combined carbon dioxide and nitric oxide lung diffusion (DLCO/DLNO) and cardiopulmonary exercise test. We measured surfactant derive protein B (immature form) as blood marker of alveolar cell function. RESULTS: We evaluated 204 consecutive post COVID-19 patients (56.5 ± 14.5 years, 89 females) 171 ± 85 days after the end of acute COVID-19 infection. We measured: forced expiratory volume (FEV1) 99 ± 17%pred, FVC 99 ± 17%pred, DLCO 82 ± 19%, DM 47.6 ± 14.8 mL/min/mmHg, Vcap 59 ± 17 mL, residual parenchymal damage at CT 7.2 ± 3.2% of lung tissue, peakVO2 84 ± 18%pred, VE/VCO2 slope 112 [102-123]%pred. Major reported symptoms were: dyspnea 45% of cases, tiredness 60% and fatigability 77%. Low FEV1, Vcap and high VE/VCO2 slope were associated with persistence of dyspnea. Tiredness was associated with high VE/VCO2 slope and low PeakVO2 and FEV1 while fatigability with high VE/VCO2 slope. SPB was fivefold higher in post COVID-19 than in normal subjects, but not associated to any of the referred symptoms. SPB was negatively associated to Vcap. CONCLUSIONS: In patients with post COVID-19, cardiorespiratory symptoms are linked to VE/VCO2 slope. In these patients the alveolar cells are dysregulated as shown by the very high SPB. The Vcap is low likely due to post COVID-19 pulmonary endothelial/vasculature damage but DLCO is only minimally impaired being DM preserved.

Improving Survival in Lymphangioleio-myomatosis: A 16-Year Observational Study in a Large Cohort of Patients.

BACKGROUND: Over the last 2 decades, great progress has been made in the understanding of the clinical aspects and pathogenesis of lymphangioleiomyomatosis (LAM), leading to publication of guidelines and approval of an effective therapy. OBJECTIVES: Aim of our study was to describe how the management and the natural history of this rare disease have changed after the publication of the ERS and American Thoracic Society/Japanese Respiratory Society guidelines and the introduction of sirolimus. METHODS: We examined 162 LAM patients followed at our center between 2001 and 2017, reporting clinical characteristics and diagnostic approach. Response to sirolimus in patients undergoing long-term treatment and mortality risk, estimated in terms of cumulative incidence taking into account organ transplantation as a competing cause of the event, were evaluated. The difference in the cumulative incidence between the patients admitted to the observation before 2011 and after 2011, year of the publication of the MILES trial for the efficacy of sirolimus, has also been estimated. RESULTS: Sixty-one patients had a histological diagnosis (22 from 2010 onward). 101 patients received a radiological diagnosis according to the guidelines criteria. Pulmonary function tests remained stable over a 3-year treatment period in patients who received sirolimus for over 12 months. The cumulative incidence of mortality after 10 years in the whole population was 25.5%. The cumulative incidence of mortality after 5 years was significantly lower in patients who entered the study since 2011 (after publication of the MILES trial) than in patients who entered the study before. CONCLUSIONS: We provide the data supporting the long-term efficacy of sirolimus therapy in a large cohort of patients with functional impairment and other manifestations of the disease. Our results also suggest that the advent of sirolimus and the publication of international guidelines changed the natural history of the disease lowering the mortality and reducing the need of invasive diagnostic techniques.

Respiratory muscle fatigue following exercise in patients with interstitial lung disease.

BACKGROUND: It is not known whether respiratory muscle fatigue occurs as a consequence of exercise in patients with interstitial lung disease (ILD) and, if so, to what extent it is related to changes in dynamic lung volumes. OBJECTIVES: To assess the development of respiratory muscle fatigue in patients with ILD and relate it to the respiratory pattern during exercise. METHODS: Sixteen ILD patients (11 women) performed incremental, symptom-limited cycle ergometry with inspiratory capacity manoeuvres used to measure changes in end-expiratory lung volume (EELV). Twitch transdia-phragmatic pressure (TwPdi) and twitch gastric pressure (TwT10Pga), in response to magnetic stimulation, were used to assess the development of fatigue. RESULTS: TwPdi did not differ significantly before and after exercise (21.8 ± 8 vs. 20.2 ± 8 cm H2O; p = 0.10), while TwT10Pga fell from 28.6 ± 18 to 25.2 ± 14 cm H2O (p = 0.02). EELV fell from 2.18 ± 0.65 to 1.91 ± 0.59 liters following exercise (p = 0.04). The fall in TwT10Pga correlated with peak oxygen uptake at peak of exercise (r = -0.52, p = 0.041), increase in heart rate (r = 0.53, p = 0.032) and with the decrease of EELV during exercise (r = 0.57, p = 0.021). Abdominal muscle fatiguers (n = 9, 56%), defined as having a ≥10% fall in TwT10Pga, had a fall in EELV of 22 ± 22% compared to 0.7 ± 8% in non-fatiguers (p = 0.016). CONCLUSION: Abdominal muscle fatigue develops during exercise in some ILD patients in association with increased expiratory muscle activity manifested by reduced EELV.

Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is an ultra-rare, slowly progressive neoplastic cystic disease, belonging to the group of PEComas. It can occur sporadically or associated to tuberous sclerosis complex disease and affects mainly women in child-birth age. Dyspnoea is the most frequent symptom referred to the time of diagnosis, however spontaneous pneumothorax may be a typical presentation associated to extrathoracic manifestations, such as renal angiomyolipomas. In the last decade, important advances in understanding molecular mechanisms underlying the LAM pathogenesis have been reached. It has allowed to obtain improvements in the research of novel biomarkers, treatment and a better management of the disease.

Comparison of clinical scoring to predict mortality risk in mild-to-moderate idiopathic pulmonary fibrosis.

BACKGROUND: During the last decade, a number of clinical scores, such as Gender-Age-Physiology (GAP) Index, TORVAN Score and Charlson Comorbidity Index (CCI), have been separately used to measure comorbidity burden in idiopathic pulmonary fibrosis (IPF). However, no previous study compared the prognostic value of these scores to assess mortality risk stratification in IPF patients with mild-to-moderate disease. METHODS: All consecutive patients with mild-to-moderate IPF who underwent high-resolution computed tomography, spirometry, transthoracic echocardiography and carotid ultrasonography at our Institution, between January 2016 and December 2018, were retrospectively analyzed. GAP Index, TORVAN Score and CCI were calculated in all patients. Primary endpoint was all-cause mortality, whereas secondary endpoint was the composite of all-cause mortality and rehospitalizations for all-causes, over medium-term follow-up. RESULTS: Seventy IPF patients (70.2±7.4 yrs, 74.3% males) were examined. At baseline, GAP Index, TORVAN Score and CCI were 3.4±1.1, 14.7±4.1 and 5.3±2.4, respectively. A strong correlation between coronary artery calcification (CAC) and common carotid artery (CCA) intima-media thickness (IMT) (r=0.88), CCI and CAC (r=0.80), CCI and CCA-IMT (r=0.81), was demonstrated in the study group. Follow-up period was 3.5±1.2 years. During follow-up, 19 patients died and 32 rehospitalizations were detected. CCI (HR 2.39, 95% CI: 1.31-4.35) and heart rate (HR 1.10, 95% CI: 1.04-1.17) were independently associated with primary endpoint. CCI (HR 1.54, 95% CI: 1.15-2.06) predicted secondary endpoint, also. A CCI ≥6 was the optimal cut-off for predicting both outcomes. CONCLUSIONS: Due to the increased atherosclerotic and comorbidity burden, IPF patients with CCI ≥6 at an early-stage disease have poor outcome over medium-term follow-up.

Prognostic role of CHA2DS2-VASc score for mortality risk assessment in non-advanced idiopathic pulmonary fibrosis: a preliminary observation.

During the last decade, the CHA2DS2-VASc score has been used for stratifying the mortality risk in both atrial fibrillation (AF) and non-AF patients. However, no previous study considered this score as a prognostic indicator in non-AF patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF). All consecutive non-AF patients with mild-to-moderate IPF, diagnosed between January 2016 and December 2018 at our Institution, entered this study. All patients underwent physical examination, blood tests, spirometry, high-resolution computed tomography and transthoracic echocardiography. CHA2DS2-VASc score, Gender-Age-Physiology (GAP) index and Charlson Comorbidity Index (CCI) were determined in all patients. Primary endpoint was all-cause mortality, while the secondary endpoint was the composite of all-cause mortality and rehospitalizations for all causes over mid-term follow-up. 103 consecutive IPF patients (70.7 ± 7.3 yrs, 79.6% males) were retrospectively analyzed. At the basal evaluation, CHA2DS2-VASc score, GAP index and CCI were 3.7 ± 1.6, 3.6 ± 1.2 and 5.5 ± 2.3, respectively. Mean follow-up was 3.5 ± 1.3 yrs. During the follow-up period, 29 patients died and 43 were re-hospitalized (44.2% due to cardiopulmonary causes). On multivariate Cox regression analysis, CHA2DS2-VASc score (HR 2.15, 95% CI 1.59-2.91) and left ventricular ejection fraction (LVEF) (HR 0.91, 95% CI 0.86-0.97) were independently associated with all-cause mortality in IPF patients. CHA2DS2-VASc score (HR 1.66, 95% CI 1.39-1.99) and LVEF (HR 0.94, 95% CI 0.90-0.98) also predicted the secondary endpoint in the same study group. CHA2DS2-VASc score > 4 was the optimal cut-off for predicting both outcomes. At mid-term follow-up, a CHA2DS2-VASc score > 4 predicts an increased risk of all-cause mortality and rehospitalizations for all causes in non-AF patients with mild-to-moderate IPF.

Recent advances in the management of pulmonary hypertension with interstitial lung disease.

Pulmonary hypertension (PH) is known to complicate various forms of interstitial lung disease (ILD), including idiopathic pulmonary fibrosis, the interstitial pneumonias and chronic hypersensitivity pneumonitis. Pathogenesis of PH-ILD remains incompletely understood, and probably has overlap with other forms of pre-capillary pulmonary hypertension. PH-ILD carries a poor prognosis, and is associated with increased oxygen requirements, and a decline in functional capacity and exercise tolerance. Despite most patients having mild-moderate pulmonary hypertension, more severe pulmonary hypertension and signs of right heart failure are observed in a subset of cases. Clinical suspicion and findings on pulmonary function, computed tomography and echocardiography are often the initial steps towards diagnosis. Definitive diagnosis is obtained by right heart catheterisation demonstrating pre-capillary pulmonary hypertension. Drugs approved for pulmonary arterial hypertension have been investigated in several randomised controlled trials in PH-ILD patients, leading to discouraging results until the recent INCREASE study. This review provides an overview of the current understanding, approach to diagnosis and recent advances in treatment.

Prognostic value of radiological index and clinical data in patients with COVID-19 infection.

During the Coronavirus-19 pandemic, chest X-ray scoring system have been validated by Al-Smadi and Toussie in this group of patients and even RALE score, previously designed for ARDS, have been used to estimate correlation with mortality. The aim of this study was to evaluate the prognostic value of As-Smadi, Tuossie and RALE scores in predicting death in the same population of patients when associated to clinical data. In this retrospective clinical study, data of patients with COVID-19, admitted to our hospital from 1st October 2020 to 31st December 2020 were collected. CXR images of each patient were analyzed with the three different scores above mentioned. 144 patients (male 96 aged 68.5 years) were included in the study. 93 patients reported a least 1 comorbidity and 36 died. The association with increasing age, presence of comorbidities, and lower hemoglobin was significantly associated with risk of death for all the regression models. When considering the radiological score, a significant effect was found for the Al Smadi and RALE scores, while no evidence of association was found for the Toussie score. The fraction of new information is 16.7% for the Al Smadi score, 12.9% for the RALE and 5.1% for the Toussie score. The improvement in the prognostic usefulness with respect to the base model is particularly interesting for the Al Smadi score. The highest c-index was also obtained by the model with the Al Smadi score.

Coronary artery calcium score is a prognostic factor for mortality in idiopathic pulmonary fibrosis.

BACKGROUND: Cardiovascular diseases are frequent in idiopathic pulmonary fibrosis (IPF) and impact on survival. We investigated the association of coronary artery calcium (CAC) score at IPF diagnosis and during mid-term follow-up, with adverse cardiovascular events and all-cause mortality. METHODS: Consecutive patients with IPF were retrospectively analyzed. Demographic data, smoking history, comorbidities and pulmonary function tests (PFTs) were recorded. All patients had at least two chest high resolution computed tomography (HRCT) performed 2 years apart. The total CAC score and visual fibrotic score were calculated and all clinically significant cardiovascular events and deaths were reported. RESULTS: The population consisted of 79 patients (57 male, mean age 74.4 ± 7.6 years); 67% of patients had a history of smoking, 48% of hypertension, 37% of dyslipidemia and 22.8% of diabetes. The visual score was 21.28 ± 7.99% at T0 and 26.54 ± 9.34% at T1, respectively (T1-T0 5.26 ± 6.13%, p< 0.001). CAC score at T0 and at T1 was 537.93 ± 839.94 and 759.98 ± 1027.6, respectively (T1-T0 224.66 ± 406.87, p< 0.001). Mean follow-up time was 2.47±1.1 years. On multivariate analysis, male sex (HR 3.58, 95% CI 1.14-11.2) and CAC score at T0 (HR 1.04, 95% CI 1.01-1.07) correlated with mortality and cardiovascular events. CAC score at T0 ≥405 showed 82% sensitivity and 100% specificity for predicting mortality and adverse cardiovascular events. CONCLUSIONS: IPF patients with a CAC score at diagnosis ≥405 have a poor prognosis over a midterm follow-up. A higher CAC score is associated with mortality and cardiovascular events.

Charlson comorbidity index, neutrophil-to-lymphocyte ratio and undertreatment with renin-angiotensin-aldosterone system inhibitors predict in-hospital mortality of hospitalized COVID-19 patients during the omicron dominant period.

Purpose: To investigate the clinical predictors of in-hospital mortality in hospitalized patients with Coronavirus disease 2019 (COVID-19) infection during the Omicron period. Methods: All consecutive hospitalized laboratory-confirmed COVID-19 patients between January and May 2022 were retrospectively analyzed. All patients underwent accurate physical, laboratory, radiographic and echocardiographic examination. Primary endpoint was in-hospital mortality. Results: 74 consecutive COVID-19 patients (80.0 ± 12.6 yrs, 45.9% males) were included. Patients who died during hospitalization (27%) and those who were discharged alive (73%) were separately analyzed. Compared to patients discharged alive, those who died were significantly older, with higher comorbidity burden and greater prevalence of laboratory, radiographic and echographic signs of pulmonary and systemic congestion. Charlson comorbidity index (CCI) (OR 1.76, 95%CI 1.07-2.92), neutrophil-to-lymphocyte ratio (NLR) (OR 1.24, 95%CI 1.10-1.39) and absence of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARBs) therapy (OR 0.01, 95%CI 0.00-0.22) independently predicted the primary endpoint. CCI ≥7 and NLR ≥9 were the best cut-off values for predicting mortality. The mortality risk for patients with CCI ≥7, NLR ≥9 and not in ACEI/ARBs therapy was high (86%); for patients with CCI <7, NLR ≥9, with (16.6%) or without (25%) ACEI/ARBs therapy was intermediate; for patients with CCI <7, NLR <9 and in ACEI/ARBs therapy was of 0%. Conclusions: High comorbidity burden, high levels of NLR and the undertreatment with ACEI/ARBs were the main prognostic indicators of in-hospital mortality. The risk stratification of COVID-19 patients at hospital admission would help the clinicians to take care of the high-risk patients and reduce the mortality.

Pulmonary Langerhans Cell Histiocytosis and Lymphangioleiomyomatosis Have Circulating Cells With Loss of Heterozygosity of the TSC2 Gene.

BACKGROUND: Lymphangioleiomyomatosis (LAM) and pulmonary Langerhans cell histiocytosis (PLCH) are cystic lung diseases in which a neoplastic cell is thought to be responsible for disease pathogenesis. The neoplastic LAM cell has mutations in the TSC genes, TSC1 or TSC2, whereas the neoplastic PLCH cell may have mutations in several genes (eg, BRAF, NRAS, MAP2K1). These mutations are not specific for PLCH and have been described in multiple cancers. TSC1 or TSC2 mutations and loss of heterozygosity (LOH) have also been described in cancers. RESEARCH QUESTION: Is TSC2 LOH specific to LAM or is it also found in PLCH? STUDY DESIGN AND METHODS: We recruited patients with LAM (n = 53) and healthy volunteers (n = 22) and compared the presence of cells with TSC2 LOH with patients with PLCH (n = 12). Blood and urine samples were collected for analysis. Fluorescence-activated cell sorting (FACS) was used to identify subpopulations of cells from blood and urine samples. We isolated CD45-CD235a-, CD45-CD235a+, and CD45+CD235a- cells from blood after density gradient separation. Cells were screened for TSC2 LOH at five microsatellites markers (ie, kg8, D16S3395, D16S3024, D16S521, D16S291). We obtained four cell subpopulations from urine (ie, CD44v6+CD9+, CD44v6+CD9-, CD44v6-CD9+, CD44v6-CD9-). RESULTS: Using FACS, cells were isolated from blood and urine from patients with PLCH that showed TSC2 LOH. Healthy volunteers did not have cells with TSC2 LOH. As a control, cells isolated from blood and urine from patients with LAM gave results similar to those reported previously. These data show that TSC2 LOH is found in patients with cystic lung diseases with potential neoplastic characteristics, and in patients with cancer. INTERPRETATION: The presence of TSC2 LOH in circulating cells is not specific for LAM. The data suggest that chromosomal abnormalities affecting the TSC2 gene are found in other diseases associated with cells having cancer-like neoplastic cells.

Dynamic hyperinflation is associated with a poor cardiovascular response to exercise in COPD patients.

BACKGROUND: Pulmonary hyperinflation has the potential for significant adverse effects on cardiovascular function in COPD. The aim of this study was to investigate the relationship between dynamic hyperinflation and cardiovascular response to maximal exercise in COPD patients. METHODS: We studied 48 patients (16F; age 68 yrs ± 8; BMI 26 ± 4) with COPD. All patients performed spirometry, plethysmography, lung diffusion capacity for carbon monoxide (TLco) measurement, and symptom-limited cardiopulmonary exercise test (CPET). The end-expiratory lung volume (EELV) was evaluated during the CPET. Cardiovascular response was assessed by change during exercise in oxygen pulse (ΔO2Pulse) and double product, i.e. the product of systolic blood pressure and heart rate (DP reserve), and by the oxygen uptake efficiency slope (OUES), i.e. the relation between oxygen uptake and ventilation. RESULTS: Patients with a peak exercise EELV (%TLC) ≥ 75% had a significantly lower resting FEV1/VC, FEF50/FIF50 ratio and IC/TLC ratio, when compared to patients with a peak exercise EELV (%TLC) < 75%. Dynamic hyperinflation was strictly associated to a poor cardiovascular response to exercise: EELV (%TLC) showed a negative correlation with ΔO2Pulse (r = - 0.476, p = 0.001), OUES (r = - 0.452, p = 0.001) and DP reserve (r = - 0.425, p = 0.004). Furthermore, according to the ROC curve method, ΔO2Pulse and DP reserve cut-off points which maximized sensitivity and specificity, with respect to a EELV (% TLC) value ≥ 75% as a threshold value, were ≤ 5.5 mL/bpm (0.640 sensitivity and 0.696 specificity) and ≤ 10,000 Hg · bpm (0.720 sensitivity and 0.783 specificity), respectively. CONCLUSION: The present study shows that COPD patients with dynamic hyperinflation have a poor cardiovascular response to exercise. This finding supports the view that in COPD patients, dynamic hyperinflation may affect exercise performance not only by affecting ventilation, but also cardiac function.

Life-threatening asthma after heroin inhalation. A case report and a review of the literature.

Heroin addiction may increase the risk of pulmonary involvement. We describe the case of a 23 year-old woman who was admitted to our unit for severe asthma attack non responsive to beta-2-agonists and acute respiratory failure, soon after heroin inhalation. The patient was successfully treated with non invasive positive pressure ventilation. Opiate inhalation can be an asthma trigger and should be considered in the care of patients with poorly controlled asthma and life-threatening asthmatic attacks.

Ultra-rare cystic disease.

Diffuse cystic lung diseases include a group of heterogeneous disorders characterised by the presence of cysts within the lung parenchyma, sometimes showing a characteristic computed tomography scan pattern that allows diagnosis. The pathogenetic mechanisms underlying cyst formation in the lung are still not clear and a number of hypotheses have been postulated according to the different aetiologies: ball-valve effect, ischaemic dilatation of small airways and alveoli related to infiltration and obstruction of small vessels and capillaries that supply the terminal bronchioles and connective tissue degradation by matrix metalloproteases. A wide number of lung cyst diseases have been classified into six diagnostic groups according to the aetiology: neoplastic, congenital/genetic, lymphoproliferative, infective, associated with interstitial lung diseases, and other causes. This article focuses on lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis and Erdheim-Chester disease, Birt-Hogg-Dubé, follicular bronchiolitis and lymphocytic interstitial pneumonia, light-chain deposition disease and amyloidosis, congenital lung disease associated with aberrant lung development and growth, and cystic lung disease associated with neoplastic lesion. These cystic diseases are epidemiologically considered as ultra-rare conditions as they affect fewer than one individual per 50 000 or fewer than 20 individuals per million. Despite the rarity of this group of disorders, the increasing use of high-resolution computed tomography has improved the diagnostic yield, even in asymptomatic patients allowing prompt and correct therapy and management without the need for a biopsy.

Smoking cessation: aspects of prevention and therapy. The activity of the Smoking Cessation Center of Parma-Italy.

The World Health Organization states that only a reduction in tobacco use would lower the number of deaths from cancer. It is possible to decrease the number of deaths by means of prevention and/or smoking cessation. Smoking cessation therapy includes both psychological support and pharmacological treatment: Nicotine Replacement Therapy (NRT), Bupropion Sustained-Release, and Varenicline. The aim of the Smoking Cessation Center of Parma is to provide instruments, methodologies and individual therapies for achieving abstinence or a decrease in tobacco use. The program of the Smoking Cessation Center consists in eight meetings. During the first meeting the smoker undergoes a medical check up, and smoking history, exhaled single breath CO and dependence of nicotine are recorded and a personal therapy is planned. During each follow-up visit (after 15 days and then at 1,2,3,6,9 and 12-month intervals) the compliance of the patient to the treatment and abstinence symptoms are assessed. Since 2000, we achieved tobacco abstinence in 28% of patients. Combined treatment (Bupropion/NRT) provided a higher percentage of success (39.9%).

Pulmonary hypertension and chronic lung disease: where are we headed?

Pulmonary hypertension related to chronic lung disease, mainly represented by COPD and idiopathic pulmonary fibrosis, is associated with a worse outcome when compared with patients only affected by parenchymal lung disease. At present, no therapies are available to reverse or slow down the pathological process of this condition and most of the clinical trials conducted to date have had no clinically significant impact. Nevertheless, the importance of chronic lung diseases is always more widely recognised and, along with its increasing incidence, associated pulmonary hypertension is also expected to be growing in frequency and as a health burden worldwide. Therefore, it is desirable to develop useful and reliable tools to obtain an early diagnosis and to monitor and follow-up this condition, while new insights in the therapeutic approach are explored.

Comorbidities in idiopathic pulmonary fibrosis: an underestimated issue.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fibrosing lung disease with a poor prognosis. Between 60% and 70% of IPF patients die of IPF; the remaining causes of death may be due to comorbidities occurring in this ageing population. Interest in the role played by comorbidities in IPF has increased in the past few years. The optimal clinical management of IPF is multifaceted and not only involves antifibrotic treatment, but also vaccinations, oxygen supplementation, evaluation of nutritional status as well as psychological support and patient education. Symptom management, pulmonary rehabilitation, palliative care and treatment of comorbidities represent further areas of clinical intervention. This review analyses the major comorbidities observed in IPF, focusing on those that have the greatest impact on mortality and quality of life (QoL). The identification and treatment of comorbidities may help to improve patients' health-related QoL (i.e. sleep apnoea and depression), while some comorbidities (i.e. lung cancer, cardiovascular diseases and pulmonary hypertension) influence survival. It has been outlined that gathering comorbidities data improves the prediction of survival beyond the clinical and physiological parameters of IPF.