Predictive role of natural killer cells in bronchoalveolar lavage fluid of patients with sarcoidosis.

Sarcoidosis is a rare granulomatous disease of unknown aetiology belonging to the wide group of interstitial lung diseases.). Although the limitlessness of BAL fluid is debated, it remains one of the best matrices for studying the pathogenesis of sarcoidosis. Natural killer (NK) cells have been described in BAL fluid from sarcoidosis patients. Elevated NK cells in BAL fluid from sarcoidosis patients have been found to be associated with poor outcomes. In this study, NK cells were evaluated in BAL samples from sarcoidosis patients at the time of diagnosis and associated with clinical characteristics in order to evaluate their prognostic role. Of the 276 patients suspected to have sarcoidosis on the basis of clinical and radiological findings, 248 had a final diagnosis of sarcoidosis. Clinical parameters, Scadding stage, and extrapulmonary localization were collected in a database. It resulted in fibrotic sarcoidosis patients being associated with an increase in lymphocyte percentages in BAL samples, particularly NK cells when compared with other groups. From ROC analysis, NK cell percentages in BAL samples resulted as being the best predictive markers in discriminating stage 4 of sarcoidosis from other RX stages (AUC=0.85, p<0.0001). Furthermore, after the stratification of patients on the basis of the number of extrapulmonary localizations, patients with an higher number of extrapulmonary localizations also showed higher percentages of NK cells in BAL fluid. In conclusion, NK cell percentages in BAL fluid can be considered a good prognostic marker of fibrotic phenotypes of sarcoidosis and involvement of other organs, although their diagnostic utility was poor.

Influence of allergic status and nasal polyposis on long-term Benralizumab response in eosinophilic severe asthma.

Objective: It is unclear whether Benralizumab effectiveness in severe eosinophilic asthma can be influenced by nasal polyposis (NP) or allergic status associations. We evaluated whether Benralizumab long-term efficacy in asthma outcomes could be different in subjects with atopy (SAEA) compared to the effectiveness in those without allergies (SNAEA) and in individuals with NP compared to those without NP. Methods: This observational retrospective study considered 95 consecutive patients divided into allergic (SAEA; n:65[68.4%]; skin prick tests positive [SPT] and/or IgE values ≥100 UI/mL), and non-allergic (SNAEA; n:30[31.6%], SPT negative and normal IgE levels<100 UI/mL). Overall population was also divided into two groups according to NP presence (NP+:39[41%] and NP-:56[59%]). Benralizumab treatment mean was19.7±7.2 months (range 12-35). Results: No differences in Benralizumab effectiveness were found in asthma outcomes in patients with/without NP. SNOT-22 improvement was higher in NP+ (-22±24) compared to NP- groups (6.33±15.5;p=0.055). FEV1 (16.33±19.22%), ACT(7.45±3.95) increases and frequency of SABA use (3.37±4.99) reduction were higher in SAEA compared to what obtained in non-allergic subjects (FEV1:8.15±15.6%,p=0.043; ACT:4.89±3.57,p=0.005; SABA use:-1.16±1.84;p=0.015). 93.8% of SAEA patients whereas only 72.2% of SNAEA individuals reduced OC doses at least half after Benralizumab (p=0.035). These results were partially confirmed by linear regression models showing associations between allergic status and FEV1, ACT and SABA use changes (ß=8.37;p=0.048, ß=2.056;p=0.033 and ß=-2.184;p=0.042 respectively). Conclusion: Benralizumab effectiveness in asthma appears to be independent of NP presence. The allergic eosinophilic disease, compared to just eosinophilic asthma, may be a more severe phenotype. Benralizumab may have greater efficacy in SAEA on some outcomes.

Prognostic bioindicators in severe COVID-19 patients.

BACKGROUND: Severe acute respiratory syndrome caused by novel coronavirus 2 (SARS-CoV-2) emerged in Wuhan (China) in December 2019. Here we evaluated a panel of biomarkers to phenotype patients and to define the role of immuno-inflammatory mediators as biomarkers of severity. MATERIALS AND METHODS: Serum samples were obtained from 24 COVID-19 patients on admission to hospital, before any treatment or infusion of intravenous steroids or invasive ventilation. KL-6 IL-6 and C-peptide were measured by chemiluminescent enzyme immunoassay. IL-6 assay was validated for accuracy and precision. The validity of variables used to distinguish severe from mild-to-moderate patients was assessed by areas under curves (AUC) of the receiver operating characteristic (ROC) and logistic regression was performed to combine parameters of the two groups. RESULTS: In the severe group, IL-6, CRP and KL-6 concentrations were significantly higher than in mild-to-moderate patients. KL-6, IL-6 and CRP concentrations were directly correlated with each other. ROC curve analysis of the logistic regression model including IL-6, KL-6 and CRP showed the best performance with an AUC of 0.95. CONCLUSIONS: Besides corroborating previous reports of over-expression of IL-6 in severe COVID-19 patients requiring mechanical ventilation, analytical determination of other mediators showed that IL-6 concentrations were correlated with those of KL-6 and CRP. The combination of these three prognostic bioindicators made it possible to distinguish severe COVID-19 patients with poor prognosis from mild-to-moderate patients.

Incidence and risk factors for respiratory tract bacterial colonization and infection in lung transplant recipients.

To evaluate incidence of and risk factors for respiratory bacterial colonization and infections within 30 days from lung transplantation (LT). We retrospectively analyzed microbiological and clinical data from 94 patients transplanted for indications other than cystic fibrosis, focusing on the occurrence of bacterial respiratory colonization or infection during 1 month of follow-up after LT. Thirty-three percent of patients developed lower respiratory bacterial colonization. Bilateral LT and chronic heart diseases were independently associated to a higher risk of overall bacterial colonization. Peptic diseases conferred a higher risk of multi-drug resistant (MDR) colonization, while longer duration of aerosol prophylaxis was associated with a lower risk. Overall, 35% of lung recipients developed bacterial pneumonia. COPD (when compared to idiopathic pulmonary fibrosis, IPF) and higher BMI were associated to a lower risk of bacterial infection. A higher risk of MDR infection was observed in IPF and in patients with pre-transplant colonization and infections. The risk of post-LT respiratory infections could be stratified by considering several factors (indication for LT, type of LT, presence of certain comorbidities, and microbiologic assessment before LT). A wider use of early nebulized therapies could be useful to prevent MDR colonization, thus potentially lowering infectious risk.

Right cardiac involvement in lung diseases: a multimodality approach from diagnosis to prognostication.

Lung diseases are amongst the main healthcare issues in the general population, having a high burden of morbidity and mortality. The cardiovascular system has a key role in patients affected by respiratory disorders. More specifically, the right ventricle (RV) enables the impaired lung function to be overcome in an initial stage of disease process, reducing the severity of dyspnoea. In addition, two of the main causes of death in this setting are RV failure and sudden cardiac death (SCD). Echocardiography is regarded as a useful and easily available tool in assessing RV function. Several noninvasive echocardiographic parameters of elevated pulmonary pressures and RV function have been proposed. The combination of different parameters and imaging methods is paramount and researches regarding RV impairment using these indices has been specifically addressed in relation to the chronic obstructive and restrictive lung disease in order to guide the clinicians in the management of these patients. Cardiac involvement in lung diseases is often observed, and RV changes are reported also in early stages of pulmonary diseases. The role of right ventricle in chronic respiratory disease patients has to be evaluated in detail to describe the response to therapy and the degree of disease progression through multimodality and advanced imaging techniques. The aim of this review is to describe the different pathophysiological mechanisms of cardiac impairment in primary lung disease (such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and sarcoidosis) and to summarize the role of cardiac multimodality imaging in the diagnosis and the prognosis of these diseases.

Effects of rituximab therapy on B cell differentiation and depletion.

Rituximab is a human/murine chimeric anti-CD20 monoclonal antibody. It is largely used to treat B cell malignancies and has become standard in the management of B cell­mediated diseases such as rheumatoid arthritis and granulomatosis with polyangitis. The effects of rituximab need to be monitored by B cell phenotyping. Evaluate possible surface markers for monitoring B cell development in response to rituximab treatment. This review discusses the literature on the B cell surface markers analysed by flow cytometry in patients treated with rituximab. A panel of biomarkers of response to treatment to monitor by flow cytometry is also suggested. B cell phenotyping is useful to predict clinical relapses after rituximab treatment. The proposed panel of biomarkers includes CD38++CD24++IgD+/- immature B cells and IgD-CD38+/- memory B cells. In responders, Th1/Th2 balance and tolerance cells (CD4+CD25+CD127-/low Treg cells and CD19+CD24hiCD38hi Breg cells) tend to be restored after rituximab therapy. Furthermore, in responder patients, indirect depletion of CD19+/-CD27++CD38++ preplasma cells can be proposed as a predictor of response. Flow cytometric analysis of samples from patients treated with rituximab is a useful strategy to stratify patients according to response to treatment. Identification of B cell differentiation stages by means of a specific flow cytometry panel could improve monitoring of rituximab effects and enable non-responders to be distinguished from good responders.

Omalizumab treatment in Samter's triad: case series and review of the literature.

OBJECTIVE: Samter's triad is the combination of asthma, aspirin sensitization, and nasal polyposis. Few data are available on the use of omalizumab in this disease. The study aimed to describe the impact of omalizumab on clinical and functional parameters and the quality of life of a series of patients with Samter's triad. Moreover, we aimed to provide a review of the literature on this topic. PATIENTS AND METHODS: We retrospectively described four patients with Samter's triad undergoing omalizumab therapy. Clinical, functional, and immunological data of these patients were collected at baseline and follow-up. RESULTS: Reduction of asthma exacerbations and salbutamol rescue therapy were observed in all patients after anti-IgE treatment together with an improvement in the quality of life. A significant improvement in FEV1, FVC, and FEF25-75 was observed. No major side-effects were observed. A total of 14 studies regarding omalizumab in aspirin-exacerbated respiratory diseases were included in the review, comprising 78 patients. All studies reported a good efficacy in improving asthma control; restoration of aspirin tolerance was repeatedly reported. CONCLUSIONS: The results of our case series and review of the literature suggest that omalizumab effectively improves asthma control, lung function tests, and quality of life in patients with Samter's triad.

NK and NKT-like cells in granulomatous and fibrotic lung diseases.

ABTRACT: Background The pathogenetic and regulatory roles of natural killer (NK) and natural killer T-like cells in interstitial lung diseases (ILDs), fibrotic and granulomatous of unknown etiology are unclear. Objectives Here we investigated NK and NKT-like cells in peripheral blood (PB) and Bronchoalveolar lavage (BAL) from patients with ILDs. Method 190 patients (94 male mean age 61 ± 14.3 years) and 8 controls undergoing bronchoscopy for ILD diagnostic work-up were enrolled consecutively; 115 patients sarcoidosis, 24 chronic fibrotic hypersensitivity pneumonitis and 43 patients other ILDs [32 idiopathic pulmonary fibrosis (IPF) and 11 non-specific interstitial pneumonia (NSIP)]. PB and BAL were processed by flow cytometry using monoclonal antibodies to differentiate NK and NKT-like cells. Results NK% in BAL was significantly different among ILDs (p = 0.02). Lower NK% was observed in BAL from sarcoidosis than other ILDs (p < 0.05). Similar findings were observed for NKT-like, whereas no differences were found for PB NK%. Difference of NK% was observed between BAL and PB in all groups (p < 0.001). Sarcoidosis patients reported the best area under the curve for NKT-like (AUC = 0.678, p = 0.0015) and NK cells (AUC = 0.61, p = 0.001). In the IPF-NSIP subgroup, NK% cell was inversely correlated with FVC% (r = - 0.34, p = 0.03) and DLCO% (r = - 0.47, p = 0.0044). Conclusions NK and NKT-like were expressed differently in BAL from patients with different ILD and were significantly depleted in sarcoidosis respect to other ILDs. This suggests that these cells may play a protective role in the pathogenesis of sarcoidosis.

Pirfenidone and Nintedanib in idiopathic pulmonary fibrosis: Real-life experience in an Italian referral centre.

BACKGROUND: Idiopathic pulmonary fibrosis has a median survival time after diagnosis of 2-5 years. The main goal of treating IPF is to stabilize or reduce the rate of disease progression. Nintedanib and Pirfenidone have been a breakthrough in the management of IPF. Here we evaluated the effectiveness of Pirfenidone and Nintedanib in a population of IPF patients diagnosed in the last 12 months at Florence ILD Referral Centre. METHODS: In the last 12 months, 82 IPF patients (66 male, mean age 78.3±23.8 years) were diagnosed and started antifibrotic therapy with Pirfenidone or Nintedanib. Their clinical and functional details were analyzed retrospectively at time 0 and after 6 and 12 months of therapy. RESULTS: The median age of the patients treated with Nintedanib was higher than that of the Pirfenidone group (p<0.0001). The most common symptoms at disease onset were exertional dyspnoea and dry cough with no differences between the two groups (p<0.05). All IPF patients manifested bibasal crackles at the time of diagnosis. No significant differences in FVC, FEV1, TLC and DLCO were found at time 0 or after 6 months between patients treated with Pirfenidone and Nintedanib (p>0.05). After 1 year, lung function test parameters of patients treated with Pirfenidone had remained stable from baseline. DISCUSSION: This study emphasizes that both antifibrotic drugs appeared to be a good therapeutic choice in terms of functional stabilization, also in older patients.

Comparative proteomic analysis of bronchoalveolar lavage of familial and sporadic cases of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive deterioration of the alveolar integrity. Among IPF identified phenotypes, that of familial (f-)IPF is usually associated with several gene mutations which are seldom observed in sporadic (s-)IPF. This study aimed at investigating the molecular patterns and variability in f-IPF and s-IPF patients through a differential proteomic analysis. Protein patterns of bronchoalveolar lavage fluid (BALF) samples from 10 familial and 17 sporadic IPF patients were compared using 2D electrophoresis and mass spectrometry. Principal component analysis (PCA) was applied to proteomic data and an enrichment analysis was also performed to characterize specific pathogenic mechanisms and to identify potential biomarkers. BALF samples from f-IPF showed 87 protein spots differentially expressed than those from s-IPF samples; once identified, these spots revealed 22 unique proteins. The functional analysis showed that the endothelial reticulum stress probably plays a central pathogenetic role in f-IPF with an up-regulation of proteins involved in wounding and immune responses, coagulation system, and ion homeostasis. Up-regulated proteins in the s-IPF group were those involved in the oxidative stress response. PCA analysis of differentially expressed proteins clearly distinguished f-IPF from s-IPF patients, and in agreement with radiological and histological patterns, pointed out a higher heterogeneity in f-IPF than s-IPF samples. The 'Slit/Robo signaling', 'clathrin-coated vesicle' and 'cytoskeleton remodelling', were extrapolated by 'pathways analysis' and the results of 'diseases (by biomarkers)' highlighted a 'connective tissue and autoimmune disease', two aspects of increasing interest in IPF.

A functional proteomics approach to the comprehension of sarcoidosis.

Pulmonary sarcoidosis (Sar) is an idiopathic disease histologically typified by non-caseating epitheliod cell sarcoid granulomas. A cohort of 37 Sar patients with chronic persistent pulmonary disease was described in this study. BAL protein profiles from 9 of these Sar patients were compared with those from 8 smoker (SC) and 10 no-smoker controls (NSC) by proteomic approach. Principal Component Analysis was performed to clusterize the samples in the corresponding conditions highlighting a differential pattern profiles primarily in Sar than SC. Spot identification reveals thirty-four unique proteins involved in lipid, mineral, and vitamin Dmetabolism, and immuneregulation of macrophage function. Enrichment analysis has been elaborated by MetaCore, revealing 14-3-3ε, α1-antitrypsin, GSTP1, and ApoA1 as "central hubs". Process Network as well as Pathway Maps underline proteins involved in immune response and inflammation induced by complement system, innate inflammatory response and IL-6signalling. Disease Biomarker Network highlights Tuberculosis and COPD as pathologies that share biomarkers with sarcoidosis. In conclusion, Sar protein expression profile seems more similar to that of NSC than SC, conversely to other ILDs. Moreover, Disease Biomarker Network revealed several common features between Sar and TB, exhorting to orientate the future proteomics investigations also in comparative BALF analysis of Sar and TB.

Efficacy of pirfenidone for idiopathic pulmonary fibrosis: An Italian real life study.

BACKGROUND: In this retrospective Italian study, which involved all major national interstitial lung diseases centers, we evaluated the effect of pirfenidone on disease progression in patients with IPF. METHODS: We retrospectively studied 128 patients diagnosed with mild, moderate or severe IPF, and the decline in lung function monitored during the one-year treatment with pirfenidone was compared with the decline measured during the one-year pre-treatment period. RESULTS: At baseline (first pirfenidone prescription), the mean percentage forced vital capacity (FVC) was 75% (35-143%) of predicted, and the mean percentage diffuse lung capacity (DLCO) was 47% (17-120%) of predicted. Forty-eight patients (37.5%) had mild disease (GAP index stage I), 64 patients (50%) had moderate IPF (stage II), and 8 patients (6.3%) had severe disease (stage III). In the whole population, pirfenidone attenuated the decline in FVC (p = 0.065), but did not influence the decline in DLCO (p = 0.355) in comparison to the pre-treatment period. Stratification of patients into mild and severe disease groups based on %FVC level at baseline (>75% and ≤75%) revealed that attenuation of decline in FVC (p = 0.002) was more pronounced in second group of patients. Stratification of patients according to GAP index at baseline (stage I vs. II/III) also revealed that attenuation of decline in lung function was more pronounced in patients with more severe disease. CONCLUSIONS: In this national experience, pirfenidone reduced the rate of annual FVC decline (p = 0.065). Since pirfenidone provided significant treatment benefit for patients with moderate-severe disease, our results suggest that the drug may also be effective in patients with more advanced disease.

Exhaled nitric oxide in interstitial lung diseases.

Nitric oxide (NO) is a biomarker of nitrosative stress, which is involved in the pathogenesis of idiopathic interstitial pneumonias (IIP). This study evaluates exhaled NO levels in IIP patients and relates alveolar concentrations of NO (CalvNO) to pulmonary function test (PFT) and 6-minute walking test (6MWT) parameters. We measured fractional exhaled nitric oxide (FeNO), CalvNO and maximum conducting airway wall flux (J'awNO) in 30 healthy subjects and 30 patients with IIP (22 idiopathic pulmonary fibrosis and 8 idiopathic non-specific interstitial pneumonias). IIP patients had higher FeNO at flow rates of 50-100-150 ml/s and higher CalvNO levels than healthy controls (p<0.0001). CalvNO was significantly correlated with 6-minute walking distance (p<0.0001), recovery time (p<0.0005), TLC (p<0.001), FVC (p=0.01) and TLCO (p<0.01). IIP patients showed abnormal nitric oxide production, probably due to lung fibrosis and oxidative-mediated lung injury. CalvNO was correlated with PFT and 6MWT parameters and is proposed as a potential biomarker of lung fibrosis and exercise tolerance.

Serum analysis of coagulation factors in IPF and NSIP.

Recent literature and our previous proteomic findings prompted us to study the coagulation system in idiopathic pulmonary fibrosis (IPF), the pathogenesis of which remains unclear. The aim of this study was to compare coagulation factors in idiopathic pulmonary fibrosis and idiopathic nonspecific interstitial pneumonia (NSIP) patients and healthy controls. Thirty-three IPF patients (23 acute exacerbation and 10 stable IPF patients), 7 NSIP patients, and 44 controls were enrolled. Concentrations of D-dimer, homocysteine, functional protein C, protein C antigen, free and total protein S antigen and activity, fibrinogen and factor VIIIc were analyzed in serum of patients and controls. The lupus anticoagulant (LAC) test was also performed. Factor VIIIc levels were significantly higher in acute exacerbation IPF patients than controls (p = 0.0001) and in stable IPF patients than controls (p = 0.002). Factor VIIIc levels were higher and PT levels were lower in acute exacerbation IPF patients who died after exacerbation than in patients who survived (p = 0.04 and p = 0.003, respectively). D-dimer, fibrinogen, and homocysteine levels were also significantly higher in IPF patients than controls (p < 0.01). Protein C activity was increased in acute exacerbation IPF patients than controls (p = 0.005). The LAC test was positive in seven IPF patients and negative in controls. Procoagulant status was demonstrated in IPF patients (mainly in acute exacerbation/IPF) than controls and NSIP patients, probably due to endothelial activation and microvascular injury. These preliminary results are of interest because of their potential implications in the pathogenesis and treatment of this disease.

TLR7 Gln11Leu single nucleotide polymorphism in patients with sarcoidosis.

Sarcoidosis is a multi-factorial systemic disease with increased activity of the cellular immune components which is responsible of the formation of non-caseating granulomas in involved organs. Recent views on the etiology indicate interactions between inherited susceptibility and environmental or lifestyle factors. Concerning genes that may influence susceptibility to sarcoidosis Toll-like receptors (TLRs) may represent plausible candidates. In this present study, we investigated the X-linked TLR7 rs179008/Gln11Leu polymorphism situated on exon 3. SNP genotyping of the TLR7 exon polymorphism was performed by TaqMan allelic discrimination using the StepOnePlus™ Real-Time PCR System (Applied Biosystems). In females, the incidence of the AT genotypes of the polymorphism was significantly lower in sarcoidosis patients compared to control subjects  (P=0.0001). We could observe in control subjects a significant preponderance of the T allele of the TLR7 rs179008/Gln11Leu polymorphism compared to sarcoidosis female patients (P=0.008). In males, no significant differences between patients and controls emerged in allele frequencies of the TLR7 rs179008/Gln11Leu polymorphism. The presence of the TLR7 rs179008/Gln11Leu polymorphism in sarcoidosis may determine an alteration of TLR7 function hampering the signaling pathway involved in the onset of both cellular and humoral autoimmunity. This is consistent with the view that in some circumstances genetic mutations affecting components of the immune system can prevent systemic autoimmunity.

Towards a functional proteomics approach to the comprehension of idiopathic pulmonary fibrosis, sarcoidosis, systemic sclerosis and pulmonary Langerhans cell histiocytosis.

Bronchoalveolar lavage fluid of patients with four interstitial lung diseases (sarcoidosis, idiopathic pulmonary fibrosis, pulmonary Langerhans cell histiocytosis, fibrosis associated to systemic sclerosis) and smoker and non smoker control subjects were compared in a proteomic study. Principal component analysis was used to statistically verify the association between differentially expressed proteins and the conditions analyzed. Pathway and functional analysis by MetaCore and DAVID software revealed possible regulatory factors involved in specific "process networks" like regulation of stress and inflammatory responses. Immune response by alternative complement pathways, protein folding, Slit-Robo signaling and blood coagulation were "pathway maps" possibly associated with interstitial lung diseases pathogenesis. Four interesting proteins plastin 2, annexin A3, 14-3-3ε and S10A6 (calcyclin) were validated by Western blot analysis. In conclusion, we identified proteins that could be directly or indirectly linked to the pathophysiology of the different interstitial lung diseases. Multivariate analysis allowed us to classify samples in groups corresponding to the different conditions analyzed and based on their differential protein expression profiles. Finally, functional and pathway analysis defined the potential function and relations among identified proteins, including low abundance molecules present in the MetaCore database. BIOLOGICAL SIGNIFICANCE: This is the first study where different interstitial lung diseases such as sarcoidosis, idiopathic pulmonary fibrosis, pulmonary Langerhans cell histiocytosis, fibrosis associated to systemic sclerosis and smoker and non smoker control subjects were compared in a proteomic study to highlight their common pathways. We decided to report not only principal component analysis, used to statistically verify the association between differentially expressed proteins and the conditions analyzed, but also functional analysis general results, considering all differential proteins potentially involved in these conditions, to speculate about possible common pathogenetic pathways involved in fibrotic lung damage.

Pulmonary hypertension in idiopathic pulmonary fibrosis: prevalence and clinical progress.

The aims of the present study are to define the prevalence of pulmonary hypertension (PH) in a cohort of idiopathic pulmonary fibrosis (IPF) patients, to investigate any correlations between systolic pulmonary artery pressure (PAPs) and functional data, to evaluate clinical progress and to compare long-term survival in IPF patients with and without PH. A population of 126 IPF patients was recruited. A high prevalence of PH (39.7%, 50/126), evaluated by echocardiography on the basis of PAPs greater than 36 mmHg, was mainly observed in smokers and female patients. Regression analysis revealed a significant correlation between PAPs greater than 50 mmHg and DLCO/VA (p = 0.0294). Mean PAPs was significantly greater one year after onset of PH (p = 0.01). 11/21 patients with FVC less than 50% had a significant increase in PAPs one year after onset of PH (p = 0.02). There was a highly significant difference between survival of IPF patients with and without PH (p = 0.0001; hazard ratio = 3.56). This study revealed that PH has a high prevalence in patients with IPF and is associated with increased risk of mortality. Early diagnosis of IPF patients with pulmonary hypertension is important, so that they can be enrolled in waiting lists for lung transplant as soon as possible.

Utility of spiral CAT scan in the follow-up of patients with pulmonary Langerhans cell histiocytosis.

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare disease that occurs almost exclusively in smokers, generally young adults between 20 and 40 years old. Prognostic biomarkers of the disease are lacking. This study describes the clinical-radiological features of a group of PLCH patients and applies a semi-quantitative CT score of the chest to verify the prognostic value of radiological findings in this disease. Clinical-radiological and immunological data from 12 Caucasian patients (6M, 7 smokers and 5 ex-smokers, mean age 36±8 years) were recorded at onset and after a follow-up period of 4 years. Application of the semi-quantitative CT score revealed a prevalently cystic pattern at onset and follow-up in the majority of the patients. Patients with a prevalently nodular pattern developed cystic lesions during follow-up. Interestingly, significant correlations were found between the extent of cystic lesions and DLCO values at onset (time 0: p<0.05) and at the end of follow-up (time 1, p<0.05) and with FEV1 values at time 0 (p<0.05) and time 1 (p<0.05). Patients with progressive functional decline were those with CT evidence of severe cystic alterations. The results suggest that high resolution CT scan of the chest is mandatory for characterizing PLCH patients at diagnosis and during follow-up. The proposed CT score of the chest showed potential prognostic value.