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.

A pilot study on the use of the super dimension navigation system for optimal cryobiopsy location in interstitial lung disease diagnostics.

BACKGROUND: Transbronchial cryobiopsies has become increasingly important in the diagnostic workup for interstitial lung diseases. The rate of complications and mortality are low compared to surgical lung biopsies, but the diagnostic yield is not as high. The reason for the lower diagnostic yield could in some cases be explained by biopsies taken too centrally or in less affected areas. In this pilot study we examined the feasibility of using the electromagnetic navigation system, superDimension (SD), when performing cryobiopsies to increase the diagnostic yield. METHODS: Electromagnetic navigation bronchoscopy and cryobiopsies were performed using SD. An electromagnetic board placed on the back of the patient and a position sensor at the tip of the navigational probe created a real-time 3D reconstruction of previously acquired computer tomography images. The procedure was performed with the patients in general anesthesia using a rigid bronchoscope when performed in Florence and with a flexible bronchoscope through an orotracheal tube when performed in Aarhus. RESULTS: In total, 18 patients were included. Five patients were excluded, partly due to technical difficulties. Disposable 1.7 mm cryoprobes were used in Aarhus, and reusable 1.9 mm probes in Florence. Pneumothorax was detected in three (23%), mild hemorrhage was seen in one (8%) and moderate hemorrhage in six (46%). The biopsies contributed to the diagnosis in 11 of the patients (85%). CONCLUSION: Using superDimension electromagnetic navigation system when performing cryobiopsies is feasible. A larger prospective trial is necessary to homogenize the technique between centres and to evaluate diagnostic advantage and complications.

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.

Clinical course of IPF in Italian patients during 12 months of observation: results from the FIBRONET observational study.

BACKGROUND: FIBRONET was an observational, multicentre, prospective cohort study investigating the baseline characteristics, clinical course of disease and use of antifibrotic treatment in Italian patients with idiopathic pulmonary fibrosis (IPF). METHODS: Patients aged ≥ 40 years diagnosed with IPF within the previous 3 months at 20 Italian centres were consecutively enrolled and followed up for 12 months, with evaluations at 3, 6, 9 and 12 months. The primary objective was to describe the clinical course of IPF over 12 months of follow-up, including changes in lung function measured by % predicted forced vital capacity (FVC% predicted). RESULTS: 209 patients (82.3% male, mean age 69.54 ± 7.43 years) were enrolled. Mean FVC% predicted was relatively preserved at baseline (80.01%). The mean time between IPF diagnosis and initiation of antifibrotic therapy was 6.38 weeks; 72.3% of patients received antifibrotic therapy within the first 3 months of follow-up, and 83.9% within 12 months of follow-up. Mean FVC% predicted was 80.0% at baseline and 82.2% at 12 months, and 47.4% of patients remained stable (i.e. had no disease progression) in terms of FVC% predicted during the study. CONCLUSIONS: FIBRONET is the first prospective, real-life, observational study of patients with IPF in Italy. The short time between diagnosis and initiation of antifibrotic therapy, and the stable lung function between baseline and 12 months, suggest that early diagnosis and prompt initiation of antifibrotic therapy may preserve lung function in patients with IPF. TRIAL REGISTRATION: NCT02803580.

Pulmonary vein stenosis mimicking interstitial lung disease.

Pulmonary vein stenosis (PVS) is a rare condition, often difficult to diagnose and associated with poor prognosis at advanced stages. Lung parenchymal abnormalities are indirect evidence of PVS and can manifest as multifocal opacities, nodular lesions, unilateral effusions, and interstitial septal thickening. These can lead to erroneous diagnoses of airway disease, pneumonia, malignancies or interstitial lung disease. This review summarizes the current literature about the approach to, evaluation and management of these patients. Our case report demonstrates that PVS is an under-recognized complication of cardiovascular surgery and should be considered in all patients presenting with respiratory symptoms after a cardiac procedure.

An unusual thoracic localizations of Erdheim- Chester disease: A case report.

Erdheim- Chester disease is a rare non- Langerhans cell histiocytosis that usually involves the bones, heart, central nervous system, retroperitoneum, eyes, kidneys, skin and adrenals. Lungs are affected in up to one-half cases; at CT scan various patterns are described: interstitial disease, consolidations, micronodules and microcysts, with or without pleural involvement. We presented a case of a 59 year-old man with unusual intrathoracic manifestation of Erdheim- Chester disease. Singularities of our report are the lonely thoracic involvement at the onset of the disease and a histiocytic lesion in the posterior mediastinum.

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.

Staging systems and disease severity assessment in interstitial lung diseases.

PURPOSE OF REVIEW: In the evaluation of patients with interstitial lung diseases (ILD), treatment decisions made by clinicians, including referral for lung transplant, are based on disease severity assessment. It is crucial to quantify disease severity and numerous attempts were made to find a reliable prognostic assessment method. RECENT FINDINGS: Research focused on which severity thresholds should be used to identify patients at higher risk of death and, more recently, on prognostic composite physiologic indices and staging systems, which compared with single variables offer a number of advantages. Composite indices, such as the composite physiologic index, provide a more accurate overall estimate of disease severity and account for confounding coexisting disease process, such as pulmonary hypertension and emphysema. In idiopathic pulmonary fibrosis clinical measures have been integrated in the GAP model that strongly correlates with disease severity and mortality. Recently, the GAP model derived for idiopathic pulmonary fibrosis (IPF) has been successfully applied to non-IPF fibrotic ILD. SUMMARY: The heterogeneity in ILDs related to both disease and patient-specific factors, for many years, has impeded progress in the development of a reliable method to quantify disease severity. In the last decade, novel composite physiologic indices and staging systems have been shown to accurately reflect disease severity and reliably predict survival. Moreover, the recent finding of one informative staging system applicable to different subgroups of ILD patients has the potential to radically transform both clinical practice and research strategy in the near future of ILD.

Interstitial lung disease preceding primary biliary cirrhosis in a male patient.

A 47-year-old male was admitted with subacute onset of dry cough and fever. Chest tomography demonstrated multifocal areas of consolidation and ground glass attenuation. Cytological analysis of bronchoalveolar lavage revealed lymphocytosis and eosinophilia and anatomopathological exam of transbronchial cryobiopsy showed poorly formed non-caseous granulomas associated to interstitial lympho-plasmocitary infiltrate. The diagnosis of idiopathic granulomatous lung disease (GLD) was assumed and the patient started oral prednisolone, presenting clinical, functional and radiological improvement. Two years later, the patient was diagnosed with primary biliary cirrhosis (PBC). At this time, it was possible to associate GLD with the autoimmune hepatobiliary disease. Clinical, epidemiological and pathological aspects of this uncommon case of interstitial lung disease as first presentation of PBC in a male patient are discussed.

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.