The role of lung biopsy for diagnosis and prognosis of interstitial lung disease in systemic sclerosis: a systematic literature review.

BACKGROUND: The prognostic and theragnostic role of histopathological subsets in systemic sclerosis interstitial lung disease (SSc-ILD) have been largely neglected due to the paucity of treatment options and the risks associated with surgical lung biopsy. The novel drugs for the treatment of ILDs and the availability of transbronchial cryobiopsy provide a new clinical scenario making lung biopsy more feasible and a pivotal guide for treatment. The aim of our study was to investigate the usefulness of lung biopsy in SSc ILD with a systematic literature review (SLR). METHODS: PubMed, Embase and Cochrane databases were searched up to June 30, 2023. Search terms included both database-specific controlled vocabulary terms and free-text terms relating to lung biopsy and SSc-ILD diagnostic and prognosis. The SLR was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Studies were selected according to the PEO (population, exposure, and outcomes) framework and Quality assessment of diagnostic accuracy studies (QUADAS) were reported. RESULTS: We selected 14 articles (comprising 364 SSc-ILD patients). The paucity and heterogeneity of the studies prevented a systematic analysis. Diffuse cutaneous SSc was present in 30-100% of cases. Female predominance was observed in all studies (ranging from 64 to 100%). Mean age ranged from 42 to 64 years. Mean FVC was 73.98 (+/-17.3), mean DLCO was 59.49 (+/-16.1). Anti-Scl70 antibodies positivity was detected in 33% of cases (range: 0-69.6). All patients underwent surgical lung biopsies, and multiple lobes were biopsied in a minority of studies (4/14). Poor HRCT-pathologic correlation was reported with HRCT-NSIP showing histopathologic UIP in up to 1/3 of cases. Limited data suggest that SSc-UIP patients may have a worse prognosis and response to immunosuppressive treatment compared to other histopathologic patterns. CONCLUSIONS: The data from this SLR clearly show the paucity and heterogeneity of the studies reporting lung biopsy in SSc ILD. Moreover, they highlight the need for further research to address whether the lung biopsy can be helpful to refine prognostic prediction and guide therapeutic choices.

EBUS-guided cryobiopsy in the diagnosis of thoracic disorders.

BACKGROUND: Endobronchial Ultrasound (EBUS) has emerged as a crucial tool for diagnosing intrathoracic disorders, particularly in the staging of lung cancer. However, its diagnostic capabilities in the context of benign and rare diseases remain a subject of debate. AIM: to investigate the diagnostic yield and safety of EBUS-transbronchial mediastinal cryobiopsy (EBUS-TMC) in comparison to EBUS-transbronchial needle aspiration (TBNA) for a broad spectrum of intrathoracic diseases. METHODS: a single-centre retrospective observational study conducted on 48 patients who underwent both EBUS-TBNA and endobronchial ultrasound-transbronchial mediastinal cryobiopsy (EBUS-TMC) in the same procedure between August 2021 and October 2023. RESULTS: The overall diagnostic yield of EBUS-TMC surpassed that of EBUS-TBNA (95.8% vs 54.1 %), notably excelling in the diagnosis of sarcoidosis (92.8% vs 78.5 %), rare mediastinal disorders (100% vs 0 %), hyperplastic lymphadenopathy (100% vs 0 %), and lymphoproliferative disease (100% vs 0 %). No significant differences were observed in the diagnosis of NSCLC and SCLC. Samples obtained through EBUS-TMC facilitated the acquisition of NGS and immunohistochemical analyses more readily. CONCLUSION: EBUS-TMC may contribute to the precise diagnosis and subtyping of mediastinal diseases, especially lymphomas and rare mediastinal tumors, thereby reducing the number of non-diagnostic procedures.

Diagnostic yield and safety of transbronchial lung cryobiopsy for diffuse parenchymal lung diseases diagnosis: Comparison between 1.7-mm and 1.9-mm probes.

PURPOSE OF THE RESEARCH: transbronchial lung cryobiopsy has been recently accepted as a valid and less invasive alternative to surgical lung biopsy. The purpose of this randomized controlled study was to evaluate, for the first time, the quality and safety of biopsy specimens obtained by using the new disposable 1.7-mm cryoprobe compared with the standard re-usable 1.9 mm cryoprobe in the diagnosis of diffuse parenchymal lung diseases. METHODS: 60 consecutive patients were prospectively enrolled and randomly assigned to two different groups: 1.9 mm (group A) and 1.7 mm (group B); primary endpoints were pathological and multidisciplinary diagnostic yield, sample size and complication rate. PRINCIPAL RESULTS: the pathological diagnostic yield of cryobiopsy was 100% in group A and 93.3% in group B (p = 0.718); cryobiopsy median diameter was 6.8 mm in group A and 6.7 mm in group B (p = 0,5241). Pneumothorax occurred in 9 patients in group A and 10 in group B (p = 0.951); mild-to-moderate bleeding in 7 cases and 9 cases in group A and B respectively (p = 0.559). No death or severe adverse events were observed. CONCLUSIONS: there was no statistically significant difference between the two groups, regarding diagnostic yield, adverse events and sampling adequacy.

Pathophysiology of light phenotype SARS-CoV-2 interstitial pneumonia: from histopathological features to clinical presentations.

Little is known about the light phenotype of SARS-CoV-2 pneumonia, which behaves in an unusual way, unlike other known respiratory diseases. We believe that the histopathological features of early COVID-19 could be considered the pathophysiological hallmark of this disease. Lung cryobiopsies show almost pristine alveoli, enlarged/hyperplasic alveolar capillaries along with dilatation of the post capillary pulmonary venules. Hypoxemia could therefore be explained by a reduction of the normal V/Q ratio, due to blood overflow around well ventilated alveoli. This could clarify typical manifestations of type L COVID-19, such as happy hypoxemia, response to awake prone positioning, response to PEEP/CPAP and platypnea orthodeoxia.

Endobronchial-ultrasound needle aspiration and endoscopic ultrasound-fine-needle aspiration in thoracic diseases.

EBUS-TBNA and EUS-FNA are minimally invasive techniques rapidly gaining ground in the non-surgical invasive diagnostic approach to thoracic diseases due to their high accuracy and low morbidity and mortality compared to surgical techniques. Moreover, in the diagnosis and staging of lung cancer the combination of the two techniques is superior to either test alone. In this review we focus on the role of EBUS-TBNA and EUS-FNA in both malignant and non-malignant thoracic diseases.

Diffuse Neuroendocrine Hyperplasia with Obliterative Bronchiolitis and Usual Interstitial Pneumonia: An Unusual "Headcheese Pattern" with Nodules.

A 74-year-old non-smoker female presented to our attention with a history of dyspnea and cough. CT scan revealed multiple areas of patchy ground glass attenuation associated to a diffuse mosaic oligoemia. Scattered bilateral subcentimetric pulmonary nodules were also present. Patient underwent a surgical lung biopsy. Specimens showed features of diffuse neuroendocrine hyperplasia, microhoneycombing, fibroblast foci. A final diagnosis of diffuse neuroendocrine hyperplasia with obliterative bronchiolitis and UIP was rendered.

The effect of anticoagulant therapy for idiopathic pulmonary fibrosis in real life practice.

BACKGROUND: IPF is a common form of interstitial lung disease for which there is no effective therapy and usually results in death. Two previous contradictory studies showed anticoagulant therapy  to be associated with both improved and worsened survival, respectively. OBJECTIVE: The objective of this retrospective cohort study was to evaluate the effect of anticoagulant therapy on the survival and disease progression of patients with idiopathic pulmonary fibrosis (IPF) in real clinical practice. METHODS: We compared the clinical characteristics, time to disease progression, incidence of acute exacerbation, and survival of 25 (20%) IPF patients receiving anticoagulant therapy to the remaining 97 IPF patients not receiving anticoagulant therapy. In addition we conducted a sensitivity analysis using as comparator a group of 25 patients matched by age, sex, functional impairment, cardiac comorbidities and pulmonary hypertension. RESULTS: Patients on anticoagulant therapy had a worse 1- and 3-year survival (84% and 53% versus 89% and 64% in the non-anticoagulant group, respectively), a difference that persisted after adjusting for age and comorbidities (hazard ratio 3.1 - 95% confidence interval, 1.4 to 7.0; p=0.006) and after comparison with the matched group (adjusted HR=4.8, 95% CI: 1.8-12.8; p=0.002). IPF patients on anticoagulant therapy had a shorter interval to disease progression ( 0.7 years versus 1.6 years, adjusted HR 2.2 -95% CI, 0.96 to 5.1; p=0.063) confirmed also in the analysis with matched subgroups (HR=2.7 (95% CI: 1.2-6.5); p=0.023). The incidence of acute exacerbations did not differ in the two groups (22% versus 23%). Two patients (8%) experienced anticoagulant treatment related complications and included an episode of hemorrhagic shock. CONCLUSION: In this retrospective study patients treated with anticoagulants had a worse survival and a shorter interval to disease progression. This support the recent finding that warfarin worsen the respiratory status and survival of IPF patients.

Diagnostic role of rapid on-site cytologic examination (ROSE) of broncho-alveolar lavage in ALI/ARDS.

BACKGROUND: While bronchoscopy should be considered in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in which the cause cannot be determined from history or clinical and laboratory data, there are no studies about the utility of rapid on-site examination (ROSE) of broncho-alveolar lavage for identification, as early as possible, of the pathological condition underlying the onset of this condition. The aim of this prospective, observational study was to evaluate the diagnostic role of ROSE of BAL in ALI/ARDS. METHODS: 71 patients with ALI/ARDS underwent bronchoalveolar lavage, and one part of the sample was examined with ROSE. The on-site report was categorized as diagnostic (specific diagnosis), presence of atypical reactive type II pneumocytes with no further comments or not diagnostic. RESULTS: ROSE of bronco-alveolar lavage yielded 29 (41%) specific diagnoses, revealed typical features of diffuse alveolar damage without a specific diagnosis in 28 patients (39%) and did not reveal a specific diagnosis in the remaining 14 cases (20%). CONCLUSIONS: The results of this study show that, in patients with ALI/ARDS, bronchoalveolar lavage with ROSE is diagnostic in 40% of cases: ROSE may therefore spare lung biopsies and improve the prognosis of patients with ARDS (immunocompetent or not) as therapy could be started or modified at a very early phase.

Pulmonary features of Birt-Hogg-Dubé syndrome: cystic lesions and pulmonary histiocytoma.

BACKGROUND: to describe clinical, radiologic and pathologic features of lung lesions in Birt-Hogg-Dubè syndrome (BHDS) (MIM 135150). METHOD: review of 12 patients of BHDS from 3 unrelated Italian families evaluated at GB Morgagni Hospital, Forlì, from 2005 to 2010. RESULTS: mean age (±SD) at diagnosis was 44.6 (±16) years, 8 (66%) were male. All three index cases presented with a history of recurrent pneumothorax and/or cystic lung lesions evaluated by CT scan request by referring pulmonary physicians, none were diagnosed to have BHDS at the time of initial pulmonary evaluation. One of the three cases was a middle-aged female patient with a clinical phenotype indistinguishable from lymphangioleiomyomatosis (LAM), characterized by cystic lung lesions and kidney angiomyolipoma. In one case of BHDS presenting with recurrent pneumothorax and a solitary lung nodule, surgical lung resection revealed a pulmonary histiocytoma. In one case a novel mutation of BHD gene was detected (c.771 del, exon 7). CONCLUSIONS: BHDS is associated with cystic lung disease largely under-recognized by pulmonary physicians and can mimic LAM and may be associated with lung tumor, pulmonary histiocytoma. In one case we found a novel mutation in exon 7, c.771 del (ref.seq. NM_144997.5) never reported before.

Idiopathic nonspecific interstitial pneumonia: an interstitial lung disease associated with autoimmune disorders?

Recent evidence suggests that idiopathic nonspecific interstitial pneumonia (iNSIP) is a distinct clinical entity amongst other idiopathic interstitial pneumonias, and some data seem to suggest a possible pathogenetic role of autoimmunity. The aim of the present study was to assess if iNSIP might represent an early lung manifestation of an autoimmune disease. After initial review of cases found in the medical records database by searching for the term "NSIP" (n = 63), 37 iNSIP cases were identified, and were re-evaluated using a dynamic integrated multidisciplinary approach. 27 cases with iNSIP were selected for the study. Mean ± sd age at first respiratory symptom was 54.2 ± 8 yrs, 70% were females, and 59% were never-smokers. At follow-up (mean ± sd 59.7 ± 29 months, range 12-138 months), autoimmune diseases occurred in 14 (52%) patients, with seven (26%) cases of autoimmune thyroiditis, six (22%) of undifferentiated connective tissue disease and three (11%) of connective tissue disease. Patients developing autoimmune diseases were older and more frequently never-smoking females. In >50% of patients diagnosed with iNSIP, evidence of autoimmune diseases develops within 2 yrs, suggesting a probable link between the clinical entity of iNSIP and autoimmune disorders.

Endobronchial ultrasound in Dieulafoy's disease of the bronchus: an additional application of EBUS.

Dieulafoy's disease is a rare vascular malformation represented by an abnormally enlarged submucosal arterial vessel. This malformation is mostly found in gastrointestinal tract causing spontaneous bleeding although a few cases have been described in the bronchial tree. Recognizing Dieulafoy's malformation is crucial for the bronchoscopist in order to avoid biopsy that can lead to a massive hemoptysis, sometimes fatal. In this case report we show the clinical utility of endobronchial ultrasound (EBUS) in the evaluation of bronchial alteration suspicious for Dieulafoy's malformation.

[Urinary acidification and rheumatoid arthritis]. / Acidificacion urinaria y artritis reumatoidea.

The aim of this study was to investigate subclinical abnormalities in renal function suggestive of incomplete distal renal tubular acidosis (DRTA) in patients with rheumatoid arthritis (RA), using the gradient between PCO2 in urine and blood (U-B PCO2 gradient), which is a simple and sensitive test. We prospectively selected 45 patients in three groups (G). G 1 (n = 15p), with RA, mean age 44 years and mean disease duration 6.5 years. G2 (n = 10 p), with RA and Sjögren's syndrome (SS), mean age 47 years and mean disease duration 6.6 years. G 3 (n = 20) healthy volunteers, no history neither renal nor rheumatic diseases, mean age 37 years. Patients in G1 and G2 had no history of concurrent disease affecting renal parenchyma, their acid-base status and renal function were normal (Creatinine clearance above 70 ml/min/1.73m2). All patients received NSAIDs but none gold salts and/or D-Penicillamine. The ability to acidify the urine was evaluated in all cases by U-B PCO2 gradient, after a 500 ml NaHCO3 continuous infusion 1 molar solution through a peripheral vein. U-B PCO2 lower than 30 was considered pathological and diagnostic for DRTA. The urinary specimen for pH and PCO2 were kept under mineral oil and processed within 5 minutes of excretion. The blood samples for PCO2 were obtained from a peripheral vein and measured after obtaining a urinary pH 7.8 or above, pH and PCO2 were measured with a BMS 3 MK2 Radiometer, Copenhagen Denmark electrode and analizer. The U-BPCO2 results were (mean 2 sd): G1 = 47 +/- 26; G2 = 49.8 +/- 8.4; G3 = 52.5 +/- 12.2. There were no statistical differences among the three groups (F = 1.228727). In the G1, a single patient presented U-B PCO2 lower than 30 (U-B PCO2 = 5), having a long active disease at the evaluation time. In G2 and G3 no gradient alterations were recorded. We conclude, in spite of the fact that U-B PCO2 gradient is a very useful and sensitive tool for detecting dRTA, that there was no correlation between incomplete type dRTA and RA or between incomplete dRTA and RA associated to SS. In addition, no association was found between NSAID intake and dRTA.