Acute and chronic eosinophilic pneumonia: an overview.

Acute and chronic eosinophilic pneumonia (AEP and CEP) include a group of rare interstitial lung diseases characterized by peripheral blood eosinophilia, increased eosinophils in bronchoalveolar lavage fluid, or eosinophilic infiltration of lung parenchyma. AEP is characterized by rapid onset, fast response to steroid treatment, and no relapse. CEP is characterized by marked tissue and peripheral blood eosinophilia, rapid response to steroid therapy, and tendency to disease recurrence. In addition, we briefly describe other eosinophilic lung diseases that must be considered in differential diagnosis of AEP and CEP. Eosinophilic pneumonias may be idiopathic or due to known causes such as medications or environmental exposure. At variance with previous reviews on this topic, a particular look in this overview was directed at pathological findings and radiological patterns.

Stem cells treatment in chronic ischemic heart disease: a narrative review.

Chronic ischemic heart disease remains a major cause of morbidity and mortality worldwide. Several trials have been performed to evaluate benefit of stem cells transplantation to restore cardiac function in short- and long-term period after myocardial infarction. This narrative review analyzes 24 clinical trials between 2005 and 2023 comprising 1824 patients with chronic heart disease without heart failure. Percent increase in left ventricular ejection fraction (LVEF) and decrease in New York Heart Association (NYHA) class at 6/12 months after stem cells transplantation are reported. Thirteen trials showed a statistically significant percent LVEF increase between 4% to 19% at 6/12 months after stem cells transplantation (p values from 0.05 to 0.0001). No significant differences in LVEF were observed between patients who underwent intracoronary or intramyocardial transplantation. NYHA class decrease from severe to mild/moderate was demonstrated in 10 trials reporting a significant LVEF increase. Patients transplanted with bone marrow and peripheral blood CD133+ stem cells showed a doubling of percentage LVEF increase in comparison to patients transplanted with CD133- cells. This narrative review reports the conflicting results on this topic. Multicenter randomized clinical trials should be performed to define the efficacy of stem cells transplantation in chronic ischemic heart disease.

Pulmonary hypertension in systemic sclerosis with usual interstitial pneumonia.

Retrospective study comparing pulmonary hypertension risk in systemic sclerosis (SSc) and non-SSc interstitial lung disease patients with usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). Retrospective analysis of 144 interstitial lung disease patients, 53 SSc (32 UIP and 21 NSIP) and 91 non-SSc (47 UIP and 44 NSIP). Pulmonary hypertension was diagnosed as pulmonary systolic artery pressure (PAPs) > 25 mmHg. All SSc and non-SSc patients with pulmonary hypertension were classified WHO Group 3. Pulmonary hypertension was identified in 21/32 (65.6%), 9/21 (42.8%), 14/47 (29.7%), and 28/44 (45.4%) SSc-UIP, SSc-NSIP, control-UIP, and control-NSIP groups, respectively. PAPs mean of SSc-UIP group was higher than control-UIP group (32.6 ± 9.8 vs 28.5 ± 6.6, p-value = 0.02). PAPs mean of SSc-NSIP group was lower than control-NSIP group (27.0 ± 7.1 vs 33.9 ± 8.8, p = 0.002). Frequency of patients with PAP > 25 mmHg in SSc-UIP group was 60% higher in comparison to control-UIP (OR = 1.62, 95% CI 0.51-5.16) and SSc-NSIP (OR = 1.60, 95% CI 0.45-5.70) groups. Logistic regression analysis estimating the linear trend per ten-unit increase in PAPs levels demonstrated an increment for the SSc-UIP group compared to the control-UIP (OR = 2.64, 95% CI 1.25-5.58, p = 0.01) and the control-NSIP (OR = 6.34, 95% CI 2.82-14.3, p < 0.001) groups. The case-control study confirms that pulmonary hypertension is frequently found in SSc patients and demonstrates, for the first time, a significant increased risk of pulmonary hypertension among SSc-UIP patients.

Early COPD diagnosis and treatment: A case report.

Chronic obstructive pulmonary disease (COPD) refers to a group of widely diffuse diseases that cause airflow blockage characterized by persistent respiratory symptoms such as dyspnea, chronic cough, recurrent wheezing, chronic sputum production, and progressive restricted airflow associated with exacerbations. COPD is the third leading cause of death worldwide and can only be treated not cured. Pulmonary function tests do not permit the identification of initial obstructive airways disease. Forced expiratory flow (FEF25-75), which calculates obstruction severity at small and medium bronchial airways levels, allows an early COPD diagnosis. We report a 72-year-old ex-smoker male not exposed to occupational risk with symptoms suggesting early COPD. Baseline pulmonary function tests were normal, except FEF25-75. The patient did not respond to the first 6 months of treatment with long-acting muscarinic antagonist (LAMA), whereas he showed a clear clinical and FEF25-75 response to 1-year treatment with LAMA associated with long-acting ß2 agonist (LABA). This clinical case report highlights the usefulness of FEF25-75 evaluation in early COPD diagnosis and monitoring and confirms the efficacy of LAMA-LABA association for small airways obstruction treatment.

Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants, genome-wide, may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ⩽0.01) within genes or regions. We also identified individual rare variants that are influential within genes and estimated the heritability of IPF on the basis of rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP heritability of IPF was estimated to be 32% (SE = 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or the development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.

Systemic sarcoidosis with pituitary adenoma.

Involvement of the nervous system with sarcoidosis is seen clinically in approximately 5-15% of cases. In most cases, lesions are localized to the leptomeninges and cranial nerves, and rarely to the pituitary gland, leading to endocrinologic abnormalities. We report on an original clinical case demonstrating the effectiveness of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scan in the diagnosis and monitoring of systemic sarcoidosis with probable pituitary involvement.

Sjögren's syndrome: a systemic autoimmune disease.

Sjögren's syndrome is a chronic autoimmune disease characterized by ocular and oral dryness resulting from lacrimal and salivary gland dysfunction. Besides, a variety of systemic manifestations may occur, involving virtually any organ system. As a result, the disease is characterized by pleomorphic clinical manifestations whose characteristics and severity may vary greatly from one patient to another. Sjögren's syndrome can be defined as primary or secondary, depending on whether it occurs alone or in association with other systemic autoimmune diseases, respectively. The pathogenesis of Sjögren's syndrome is still elusive, nevertheless, different, not mutually exclusive, models involving genetic and environmental factors have been proposed to explain its development. Anyhow, the emergence of aberrant autoreactive B-lymphocytes, conducting to autoantibody production and immune complex formation, seems to be crucial in the development of the disease. The diagnosis of Sjögren's syndrome is based on characteristic clinical signs and symptoms, as well as on specific tests including salivary gland histopathology and autoantibodies. Recently, new classification criteria and disease activity scores have been developed primarily for research purposes and they can also be useful tools in everyday clinical practice. Treatment of Sjögren's syndrome ranges from local and symptomatic therapies aimed to control dryness to systemic medications, including disease-modifying agents and biological drugs. The objective of this review paper is to summarize the recent literature on Sjögren's syndrome, starting from its pathogenesis to current therapeutic options.

In-111 octreotide SPECT/CT in the early diagnosis of pulmonary sarcoidosis: A case report.

Sarcoidosis is a granulomatous disease of unknown etiology. At present the best diagnostic imaging procedure to assess stage and activity of sarcoidosis is controversial. We report the case of a 50-year-old male admitted with a history of dyspnea and fatigue with past medical history negative for smoking, occupational and environmental risk factors. Physical examination, routine blood tests, and pulmonary function tests were normal except for hypercalciuria. A chest radiograph showed bilateral hilar lymphadenopathy. Single photon emission computed tomography and/or computed tomography (SPECT and/or CT) In-111 Octreotide (Octreoscan) scintigraphy confirmed morphologic involvement of bilateral hilar lymph nodes and a mediastinoscopy biopsy specimen provided diagnosis of pulmonary sarcoidosis (stage 0). This clinical case shows the effectiveness of In-111 Octreotide SPECT and/or CT in the early diagnosis of pulmonary sarcoidosis.

HLA-G in Allergy: Does It Play an Immunoregulatory Role?

Allergy is an inflammatory process determined by a cascade of immune events characterized by T-helper 2 lymphocytes polarization leading to interleukin-4 upregulation, IgE secretion, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, are known to play a key immunoregulatory role and their involvement in allergic diseases is supported by increasing literature data. HLA-G expression and secretion is specifically induced in peripheral blood mononuclear cells of allergic patients after in vitro incubation with the causal allergen. Elevated levels of soluble HLA-G molecules are detected in serum of patients with allergic rhinitis correlating with allergen-specific IgE levels, clinical severity, drug consumption and response to allergen-specific immunotherapy. HLA-G genetic polymorphisms confer susceptibility to allergic asthma development and high levels of soluble HLA-G molecules are found in plasma and bronchoalveolar lavage fluid of patients with allergic asthma correlating with allergen-specific IgE levels. Interestingly, allergic pregnant women have lower plasma sHLA-G levels than non-allergic women during the 3rd trimester of pregnancy and at delivery. Finally, in allergic patients with atopic dermatitis HLA-G molecules are expressed by T cells, monocytes-macrophages and Langerhans cells infiltrating the dermis. Although at present is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are specifically expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation.

HLA-G Expressing Immune Cells in Immune Mediated Diseases.

HLA-G is a HLA class Ib antigen that possesses immunomodulatory properties. HLA-G-expressing CD4+ and CD8+ T lymphocytes, NK cells, monocytes, and dendritic cells with immunoregulatory functions are present in small percentages of patients with physiologic conditions. Quantitative and qualitative derangements of HLA-G+ immune cells have been detected in several conditions in which the immune system plays an important role, such as infectious, neoplastic, and autoimmune diseases as well as in complications from transplants and pregnancy. These observations strongly support the hypothesis that HLA-G+ immune cells may be implicated in the complex mechanisms underlying the pathogenesis of these disorders.

Early Disease and Low Baseline Damage as Predictors of Response to Belimumab in Patients With Systemic Lupus Erythematosus in a Real-Life Setting.

OBJECTIVE: To investigate predictors of response, remission, low disease activity, damage, and drug discontinuation in patients with systemic lupus erythematosus (SLE) who were treated with belimumab. METHODS: In this retrospective study of a multicenter cohort of SLE patients who received intravenous belimumab, the proportion of patients who achieved remission, low disease activity, and treatment response according to the SLE Responder Index 4 (SRI-4) was determined, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) was used to score disease damage yearly over the follow-up. Predictors of outcomes were analyzed by multivariate logistic regression with the results expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: The study included 466 patients with active SLE from 24 Italian centers, with a median follow-up period of 18 months (range 1-60 months). An SRI-4 response was achieved by 49.2%, 61.3%, 69.7%, 69.6%, and 66.7% of patients at 6, 12, 24, 36, and 48 months, respectively. Baseline predictors of response at 6 months included a score of ≥10 on the SLE Disease Activity Index 2000 (SLEDAI-2K) (OR 3.14 [95% CI 2.033-4.860]) and a disease duration of ≤2 years (OR 1.94 [95% CI 1.078-3.473). Baseline predictors of response at 12 months included a score of ≥10 on the SLEDAI-2K (OR 3.48 [95% CI 2.004-6.025]) and an SDI score of 0 (OR 1.74 [95% CI 1.036-2.923]). Baseline predictors of response at 24 months included a score of ≥10 on the SLEDAI-2K (OR 4.25 [95% CI 2.018-8.940]) and a disease duration of ≤2 years (OR 3.79 [95% CI 1.039-13.52]). Baseline predictors of response at 36 months included a score of ≥10 on the SLEDAI-2K (OR 14.59 [95% CI 3.54-59.79) and baseline status of current smoker (OR 0.19 [95% CI 0.039-0.69]). Patients who were in remission for ≥25% of the follow-up period (44.3%) or who had low disease activity for ≥50% of the follow-up period (66.1%) accrued significantly less damage (P = 0.046 and P = 0.007). A baseline SDI score of 0 was an independent predictor of achieving low disease activity in ≥50% of the follow-up period and remission in ≥25% of the follow-up period. Our findings suggest that the lower the baseline damage, the greater the probability of achieving remission over the course of ≥25% of the follow-up. Further, there was a negative association between the number of flares reported prior to belimumab initiation and the frequency of belimumab discontinuation due to inefficacy (P = 0.009). CONCLUSION: In patients with active SLE and low damage at baseline, treatment with belimumab early in the disease may lead to favorable outcomes in a real-life setting.

Diagnosis of an unusual case of idiopathic mediastinal fibrosis by 18F-FDG PET/CT.

Diagnosis of idiopathic mediastinal fibrosis was done by exclusion in a 54-year-old woman with dyspnoea, chest pain, cough and fatigue showing positivity of 2-deoxy-2-[18F]fluoro-D-glucose positron-emission tomography/computed tomography total body imaging which turned out to normal after six and eighteen months of prednisone and pirfernidone treatment.

Neutrophil Extracellular Traps Profiles in Patients with Incident Systemic Lupus Erythematosus and Lupus Nephritis.

OBJECTIVE: Neutrophil extracellular traps (NET) expose modified antigens for autoantibodies in vasculitis. Little is known about levels and removal pathways of NET in systemic lupus erythematosus (SLE), especially in lupus nephritis (LN). We determined circulating levels and defined NET removal in large subsets of patients with incident SLE (iSLE), some of whom had new-onset nephritis. METHODS: Serum levels of NET (ELISA), DNase1/DNase1L3 (ELISA), and DNase activity (functional assay) were determined in 216 patients with iSLE [103 had incident LN (iLN)], in 50 patients with other primary glomerulonephritis, and in healthy controls. Ex vivo NET production by neutrophils purified from a random selection of patients was quantified as elastase/DNA release and by immunofluorescence techniques. RESULTS: Serum NET levels were very high in iSLE/iLN compared to all groups of controls and correlated with anti-dsDNA, C3-C4, and proteinuria; iLN had the highest levels. DNase activity was decreased in iLN compared to SLE (20% had one-half DNase activity) despite similar serum levels of DNase1/DNase1L3. In these cases, pretreatment of serum with protein A restored DNase efficiency; 1 patient was homozygous for a c.289_290delAC variant of DNASE1L3. Ex vivo NET production by neutrophils purified from LN, SLE, and normal controls was similar in all cases. CONCLUSION: Patients with iLN have increased circulating NET and reduced DNase activity, the latter being explained by the presence of inhibitory substances in circulation and/or by rare DNase1L3 mutations. Accumulation of NET derives from a multifactorial mechanism, and is associated and may contribute to disease severity in SLE, in particular to renal lesions. (Clinical trial registration: The Zeus study was registered at ClinicalTrials.gov, study number NCT02403115).