Pneumomediastinum in COVID-19: Risk factors and outcomes from a multicentre case-control study.

BACKGROUND: An increased incidence of pneumomediastinum has been observed among patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. The study aimed to identify risk factors for COVID-19-associated pneumomediastinum and investigate the impact of pneumomediastinum on clinical outcomes. METHODS: In this multicentre retrospective case-control study, we included consecutive patients with COVID-19 pneumonia and pneumomediastinum hospitalized from March 2020 to July 2020 at ten centres; then, we identified a similarly sized control group of consecutive patients hospitalized with COVID-19 pneumonia and respiratory failure who did not develop pneumomediastinum during the same period. Clinical, laboratory, and radiological characteristics, as well as respiratory support and outcomes, were collected and compared between the two groups. Risk factors of pneumomediastinum were assessed by multivariable logistic analysis. RESULTS: Overall 139 patients with pneumomediastinum and 153 without pneumomediastinum were analysed. Lung involvement ≥75 %, consolidations, body mass index (BMI) < 22 kg/m2, C-reactive protein (CRP) > 150 mg/L, D-dimer >3000 ng/mL FEUs, and smoking exposure >20 pack-year were all independently correlated with the occurrence of pneumomediastinum. Patients with pneumomediastinum had a longer hospital stay (mean ± SD 31.2 ± 20.2 days vs 19.6 ± 14.2, p < 0.001), higher intubation rate (73/139, 52.5 % vs 27/153, 17.6 %, p < 0.001), and in-hospital mortality (68/139, 48.9 % vs 36/153, 23.5 %, p < 0.001) compared to controls. CONCLUSIONS: Extensive lung parenchyma involvement, consolidations, low BMI, high inflammatory markers, and tobacco exposure are associated with a greater risk of pneumomediastinum in COVID-19 pneumonia. This complication significantly worsens the outcomes.

Effectiveness and safety of Argon Plasma Coagulation in patients with haemoptysis caused by an endobronchial malignancy.

BACKGROUND: Patients with central neoplasms and haemoptysis show low survival rates. Symptom control without recurrence 48 hours after bronchoscopic interventions may improve the prognosis of these patients. Bronchoscopic Argon Plasma Coagulation (APC) is a useful technique for endobronchial management of haemoptysis in patients with central malignancies. Nevertheless, limited data are available in the literature on its efficacy and safety and the main predictors of success are still unclear. MATERIALS AND METHODS: An observational, prospective, single-center cohort study was carried out to assess the efficacy (i.e. immediate bleeding cessation without recurrence during the following 48 hours) of bronchoscopic APC in the treatment of patients with haemoptysis caused by endobronchial malignancies and the main predictors of success. RESULTS: A total of 76 patients with median age 75 years (IQR: 65-79) were enrolled. 67 (88.2%) patients had bleeding cessation without recurrence 48 hours after bronchoscopic APC. A low rate of non-serious adverse events (5.3%) was recorded and a low (7.6%) recurrence rate of haemoptysis at 3.5 months after the procedure was also shown. No clinical, demographic and endoscopic variables related to a successful procedure at 48 hours were found. CONCLUSIONS: This study demonstrates that bronchoscopic APC is an effective procedure in the treatment of patients with haemoptysis caused by endobronchial malignancies, regardless of the clinical characteristics of the patients, the endoscopic and histological features of the neoplasm and the severity of the symptom. Furthermore, it shows a low rate of complications and long-term efficacy in bleeding control.

The current practice in the diagnostic work-up of patients with hemoptysis of unknown etiology: an international survey.

BACKGROUND: Hemoptysis is a challenging and potentially life-threatening medical condition. The most appropriate diagnostic work-up is debated and several diagnostic approaches are implemented worldwide. METHODS: An international, online survey was carried out to investigate the current practice of the diagnostic work-up of patients with hemoptysis of unknown etiology. RESULTS: Overall, 604 physicians responded to the survey. At baseline, chest X-ray was suggested as the first diagnostic investigation by 342 (56.6%) participants. Computed tomography (CT) was suggested in each patient with non- and life-threatening hemoptysis by 310 (51.3%) and 526 (87.1%) respondents, respectively. Contrast-enhanced CT is the currently preferred technique (333, 55.1%). In case of patchy ground glass opacities and negative CT, 287 (47.5%) and 222 (36.8%) participants, respectively, would always offer bronchoscopy. Otorhinolaryngological evaluation was mostly suggested in case of suspected upper airways bleeding before other investigations (212, 35.1%). A follow-up was recommended for idiopathic hemoptysis by the majority of the participants (316, 52.3%). A multidisciplinary assessment is deemed crucial for each patient with life-threatening hemoptysis (437, 72.4%). CONCLUSIONS: Chest X-ray and contrast-enhanced CT are currently preferred as the first diagnostic investigations, regardless of hemoptysis severity. Bronchoscopy is suggested in case of negative radiological examination and when CT shows only ground glass opacities. Otorhinolaryngological evaluation is advised before any other investigations when upper airways bleeding is suspected. Patients with idiopathic hemoptysis are suggested to undergo a clinical follow-up and in case of life-threatening bleeding a multidisciplinary assessment is deemed crucial. Due to the heterogeneous approaches a consensus statement would be needed.

Exploring the Potential Role of Metabolomics in COPD: A Concise Review.

Chronic Obstructive Pulmonary Disease (COPD) is a pathological condition of the respiratory system characterized by chronic airflow obstruction, associated with changes in the lung parenchyma (pulmonary emphysema), bronchi (chronic bronchitis) and bronchioles (small airways disease). In the last years, the importance of phenotyping and endotyping COPD patients has strongly emerged. Metabolomics refers to the study of metabolites (both intermediate or final products) and their biological processes in biomatrices. The application of metabolomics to respiratory diseases and, particularly, to COPD started more than one decade ago and since then the number of scientific publications on the topic has constantly grown. In respiratory diseases, metabolomic studies have focused on the detection of metabolites derived from biomatrices such as exhaled breath condensate, bronchoalveolar lavage, and also plasma, serum and urine. Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy are powerful tools in the precise identification of potentially prognostic and treatment response biomarkers. The aim of this article was to comprehensively review the relevant literature regarding the applications of metabolomics in COPD, clarifying the potential clinical utility of the metabolomic profile from several biologic matrices in detecting biomarkers of disease and prognosis for COPD. Meanwhile, a complete description of the technological instruments and techniques currently adopted in the metabolomics research will be described.

Pulmonary Involvement in Recurrent Respiratory Papillomatosis: A Systematic Review.

Recurrent respiratory papillomatosis (RRP) is a non-malignant disease, characterized by the production of wart-like growths in the respiratory tract, affecting both young people and adults (juvenile-onset recurrent respiratory papillomatosis, JORRP, and adult-onset recurrent respiratory papillomatosis, AORRP, respectively). Infection caused by human papillomavirus (HPV) is known as the main factor involved in RRP development. Complications of RRP may rarely occur, including lung involvement and malignant transformation. The present systematic review aimed to evaluate the prevalence of severe complications, such as lung involvement and lung tumor in JORRP and AORRP patients, and assess the role of HPV genotypes in the progression of disease severity following the guideline for reporting systematic reviews and meta-analysis (PRISMA Statement). A total of 378 studies were found on PubMed and Scopus using the following MESH terms: "recurrent respiratory papillomatosis and lung tumor" and "pulmonary tumor and recurrent respiratory papillomatosis". Basing on inclusion and exclusion criteria, a total of 11 studies were included in the systematic review. We found a pooled prevalence of 8% (95% CI: 4-14%; I2: 87.5%) for lung involvement in RRP patients. In addition, we found a pooled risk difference of 5% in lung involvement between JORRP and AORRP (95% CI: -7-18%; I2: 85.6%, p-value: 0.41). Among patients with lung involvement, we observed a pooled prevalence of lung tumor of 4% (95% CI:1-7%; I2: 67.1%) and a pooled prevalence mortality for this group of 4% (95% CI:2-6%; I2: 0%). Overall, the positivity rate for HPV-6 and -11 in patients with RRP was 91%. Considering only cases with pulmonary involvement, the pooled prevalence for HPV-11 was 21% (95% CI: 5-45%; I2: 77.2%). Our results evidenced a low/middle risk of pulmonary involvement and lung tumor in JORRP and AORRP patients, with an increased risk for HPV-11-positive patients. Further studies should be performed to improve knowledge and adopt preventive measures to contrast the progression to severe diseases in RRP patients.

The Genetic Basis, Lung Involvement, and Therapeutic Options in Niemann-Pick Disease: A Comprehensive Review.

Niemann-Pick Disease (NPD) is a rare autosomal recessive disease belonging to lysosomal storage disorders. Three types of NPD have been described: NPD type A, B, and C. NPD type A and B are caused by mutations in the gene SMPD1 coding for sphingomyelin phosphodiesterase 1, with a consequent lack of acid sphingomyelinase activity. These diseases have been thus classified as acid sphingomyelinase deficiencies (ASMDs). NPD type C is a neurologic disorder due to mutations in the genes NPC1 or NPC2, causing a defect of cholesterol trafficking and esterification. Although all three types of NPD can manifest with pulmonary involvement, lung disease occurs more frequently in NPD type B, typically with interstitial lung disease, recurrent pulmonary infections, and respiratory failure. In this sense, bronchoscopy with broncho-alveolar lavage or biopsy together with high-resolution computed tomography are fundamental diagnostic tools. Although several efforts have been made to find an effective therapy for NPD, to date, only limited therapeutic options are available. Enzyme replacement therapy with Olipudase α is the first and only approved disease-modifying therapy for patients with ASMD. A lung transplant and hematopoietic stem cell transplantation are also described for ASMD in the literature. The only approved disease-modifying therapy in NPD type C is miglustat, a substrate-reduction treatment. The aim of this review was to delineate a state of the art on the genetic basis and lung involvement in NPD, focusing on clinical manifestations, radiologic and histopathologic characteristics of the disease, and available therapeutic options, with a gaze on future therapeutic strategies.

Pleural Mesothelioma: Advances in Blood and Pleural Biomarkers.

Pleural mesothelioma (PM) is a type of cancer that is highly related to exposure to asbestos fibers. It shows aggressive behavior, and the current therapeutic approaches are usually insufficient to change the poor prognosis. Moreover, apart from staging and histological classification, there are no validated predictors of its response to treatment or its long-term outcomes. Numerous studies have investigated minimally invasive biomarkers in pleural fluid or blood to aid in earlier diagnosis and prognostic assessment of PM. The most studied marker in pleural effusion is mesothelin, which exhibits good specificity but low sensitivity, especially for non-epithelioid PM. Other biomarkers found in pleural fluid include fibulin-3, hyaluronan, microRNAs, and CYFRA-21.1, which have lower diagnostic capabilities but provide prognostic information and have potential roles as therapeutic targets. Serum is the most investigated matrix for biomarkers of PM. Several serum biomarkers in PM have been studied, with mesothelin, osteopontin, and fibulin-3 being the most often tested. A soluble mesothelin-related peptide (SMRP) is the only FDA-approved biomarker in patients with suspected mesothelioma. With different serum and pleural fluid cut-offs, it provides useful information on the diagnosis, prognosis, follow-up, and response to therapy in epithelioid PM. Panels combining different markers and proteomics technologies show promise in terms of improving clinical performance in the diagnosis and monitoring of mesothelioma patients. However, there is still no evidence that early detection can improve the treatment outcomes of PM patients.

Mediastinal lymphadenopathies and skin lesions in a 49-year-old Sinhalese man.

Leprosy is a neglected disease sporadically reported in high-income countries. Skin lesion and peripheral nerve involvement represent most common manifestations. Mediastinal lymphadenopathy in the absence of superficial lymph nodes involvement is very rare. Atypical or rare clinical presentations of disease may delay diagnosis and therapy and cause potential life-threatening manifestations and disabilities. We describe the case of a 49-year-old Sinhalese man who was admitted to our hospital with a one-month history of peripheral neurological symptoms and skin lesions on lower limbs. CT scan showed the presence of mediastinal lymphadenopathies without lung parenchymal and superficial lymph nodes involvement. Endobronchial ultrasound-guided transbronchial needle aspiration showed the presence of granulomas while skin biopsy revealed dermo-hypodermic granulomas with perineural lymphohistiocytic inflammatory reaction. Fite-Faraco staining demonstrated the presence of acid-fast bacilli in both lymph nodal and skin biopsy and polymerase chain reaction was positive for Mycobacterium leprae. Multibacillary leprosy was then diagnosed.

SARS-CoV-2 infection sequelae on exercise response: persistent or reversible? A 2-year perspective.

Post-COVID-19 exercise capacity sequalae on oxygen utilisation and ventilatory efficiency improve over time in most patients. Cardiopulmonary exercise testing is a valuable tool to identify those who may benefit from specific rehabilitative interventions. https://bit.ly/3qFd97x.

Bronchoscopy in the post-acute phase of COVID-19: an observational study.

BACKGROUND: Bronchoscopy is a useful technique adopted in the management of patients with COVID-19. 10-40% of COVID-19 survivors experience persistent symptoms. A comprehensive description of the utility and safety of bronchoscopy in the management of patients with COVID-19 sequelae is lacking. The aim of the study was to evaluate the role of bronchoscopy in patients with suspected post-acute sequelae of COVID-19. METHODS: An observational, retrospective study was carried out in Italy. Patients requiring bronchoscopy for suspected COVID-19 sequelae were enrolled. RESULTS: 45 (21, 46.7%, female) patients were recruited. Bronchoscopy was more frequently indicated for patients with a previous critical disease. The most frequent indications were tracheal complications, mostly performed in patients who were hospitalized during the acute phase than treated at home (14, 48.3% VS. 1, 6.3%; p-value: 0.007) and persistent parenchymal infiltrates, more frequent in those treated at home (9, 56.3% VS. 5, 17.2%; p-value: 0.008). 3 (6.6%) patients after the first bronchoscopy required higher oxygen flow. Four patients were diagnosed with lung cancer. CONCLUSION: Bronchoscopy is a useful and safe technique in patients with suspected post-acute sequelae of COVID-19. The severity of acute disease plays a role in the rate and indications of bronchoscopy. Endoscopic procedures were mostly performed for tracheal complications in critical, hospitalized patients and for persistent lung parenchymal infiltrates in mild-moderate infections treated at home.

Reducing Post-Operative Alveolo-Pleural Fistula by Applying PGA-Sheets (Neoveil) after Major Lung Resection: A Historical Case-Control Study.

Alveolo-pleural fistula remains a serious post-operative complication in lung cancer patients after surgery, which is associated with prolonged hospital stay and higher healthcare costs. The aim of this study is to evaluate the efficacy of a polyglycol acid (PGA)-sheet known as Neoveil in preventing post-operative air-leak in cases of detected intra-operative air-leak after lung resection. Between 11/2021 and 7/2022, a total of 329 non-small cell lung cancer (NSCLC) patients were surgically treated in two institutions. Major lung resections were performed in 251 cases. Among them, 44 patients with significant intra-operative air-leak at surgery were treated by reinforcing staple lines with Neoveil (study group). On the other hand, a historical group (selected by propensity score matched analysis) consisting of 44 lung cancer patients with significant intra-operative air leak treated by methods other than the application of sealant patches were considered as the control group. The presence of prolonged air-leak (primary endpoint), pleural drainage duration, hospital stay, and post-operative complication rates were evaluated. The results showed that prolonged air-leak (>5 days after surgery) was not observed in study group, while this event occurred in four patients (9.1%) in the control group. Additionally, a substantial reduction (despite not statistically significant) in the chest tube removal was noted in the study group with respect to the control group (3.5 vs. 4.5, p = 0.189). In addition, a significant decrease in hospital stay (4 vs. 6 days, p = 0.045) and a reduction in post-operative complications (2 vs. 10, p = 0.015) were observed in the study group when compared with the control group. Therefore, in cases associated with intra-operative air-leak after major lung resection, Neoveil was considered a safer and more effective aerostatic tool and represents a viable option during surgical procedures.

Early outcomes of "low-risk" patients undergoing lung resection assessed by cardiopulmonary exercise testing: Single-institution experience.

Objective: Cardiopulmonary exercise testing (CPET) is currently recommended for all patients undergoing lung resection with either respiratory comorbidities or functional limitations. The main parameter evaluated is oxygen consumption at peak (VO2peak). Patients with VO2peak above 20 ml/kg/min are classified as low risk surgical candidates. The aims of this study were to evaluate postoperative outcomes of low-risk patients, and to compare their outcomes with those of patients without pulmonary impairment at respiratory function testing. Methods: Retrospective monocentric observational study was designed, evaluating outcomes of patients undergoing lung resection at San Paolo University Hospital, Milan, Italy, between January 2016 and November 2021, preoperatively assessed by CPET, according to 2009 ERS/ESTS guidelines. All low-risk patients undergoing any extent surgical lung resection for pulmonary nodules were enrolled. Postoperative major cardiopulmonary complications or death, occurring within 30 days from surgery, were assessed. A case-control study was nested, matching 1:1 for type of surgery the cohort population with control patients without functional respiratory impairment consecutively undergoing surgery at the same centre in the study period. Results: A total of 80 patients were enrolled: 40 subjects were preoperatively assessed by CPET and deemed at low risk, whereas 40 subjects represented the control group. Among the first, 4 patients (10%) developed major cardiopulmonary complications, and 1 patient (2.5%) died within 30 days from surgery. In the control group, 2 patients (5%) developed complications and none of the patients (0%) died. The differences in morbidity and mortality rates did not reach statistically significance. Instead, age, weight, BMI, smoking history, COPD incidence, surgical approach, FEV1, Tiffenau, DLCO and length of hospital stay resulted significantly different between the two groups. At a case-by-case analysis, CPET revealed a pathological pattern in each complicated patient, in spite of VO2peak above target for safe surgery. Conclusions: Postoperative outcomes of low-risk patients undergoing lung resections are comparable to those of patients without any pulmonary functional impairment; nonetheless the formers represent a dramatically different category of individuals from the latter and may harbour few patients with worse outcomes. CPET variables overall interpretation may add to the VO2peak in identifying higher risk patients, even in this subgroup.

Interventional pulmonology techniques in lung transplantation.

Lung transplantation is a key therapeutic option for several end-stage lung diseases. Interventional pulmonology techniques, mostly bronchoscopy, play a key role throughout the whole path of lung transplantation, from donor evaluation to diagnosis and management of post-transplant complications. We carried out a non-systematic, narrative literature review aimed at describing the main indications, contraindications, performance characteristics and safety profile of interventional pulmonology techniques in the context of lung transplantation. We highlighted the role of bronchoscopy during donor evaluation and described the debated role of surveillance bronchoscopy (with bronchoalveolar lavage and transbronchial biopsy) to detect early rejection, infections and airways complications. The conventional (transbronchial forceps biopsy) and the new techniques (i.e. cryobiopsy, biopsy molecular assessment, probe-based confocal laser endomicroscopy) can detect and grade rejection. Several endoscopic techniques (e.g. balloon dilations, stent placement, ablative techniques) are employed in the management of airways complications (ischemia and necrosis, dehiscence, stenosis and malacia). First line pleural interventions (i.e. thoracentesis, chest tube insertion, indwelling pleural catheters) may be useful in the context of early and late pleural complications occurring after lung transplantation. High quality studies are advocated to define endoscopic standard protocols and thus help improving long-term prognostic outcomes of lung transplant recipients.

Diffuse Pulmonary Meningotheliomatosis: Clinic-Pathologic Entity or Indolent Metastasis from Meningioma (or Both)?

Pulmonary minute meningothelial-like nodules (MMNs) are common incidental findings in surgical specimens, consisting of tiny proliferation (usually no larger than 5-6 mm) of bland-looking meningothelial cells showing a perivenular and interstitial distribution, sharing morphologic, ultrastructural, and immunohistochemical profiles with meningiomas. The identification of multiple bilateral MMNs leading to an interstitial lung disease characterized by diffuse and micronodular/miliariform patterns radiologically allows the diagnosis of diffuse pulmonary meningotheliomatosis (DPM). Nevertheless, the lung is the most common site of metastatic primary intracranial meningioma, and differential diagnosis with DPM may be impossible without clinic-radiologic integration. Herein, we report four cases (three females; mean age, 57.5 years) fitting the criteria of DPM, all incidentally discovered and histologically evidenced on transbronchial biopsy (2) and surgical resection (2). All cases showed immunohistochemical expression of epithelial membrane antigen (EMA), progesterone receptor, and CD56. Notably, three of these patients had a proven or radiologically suspected intracranial meningioma; in two cases, it was discovered before, and in one case, after the diagnosis of DPM. An extensive literature review (44 patients with DPM) revealed similar cases with imaging studies excluding intracranial meningioma in only 9% (4 of 44 cases studied). The diagnosis of DPM requires close correlation with the clinic-radiologic data since a subset of cases coexist with or follow a previously diagnosed intracranial meningioma and, thus, may represent incidental and indolent metastatic deposits of meningioma.

Exploring the Role of Immune System and Inflammatory Cytokines in SARS-CoV-2 Induced Lung Disease: A Narrative Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative pathogen of coronavirus disease 19 (COVID-19). COVID-19 can manifest with a heterogenous spectrum of disease severity, from mild upper airways infection to severe interstitial pneumonia and devastating acute respiratory distress syndrome (ARDS). SARS-CoV-2 infection may induce an over activation of the immune system and the release of high concentrations of pro-inflammatory cytokines, leading to a "cytokine storm", a recognized pathogenetic mechanism in the genesis of SARS-CoV-2-induced lung disease. This overproduction of inflammatory cytokines has been recognized as a poor prognostic factor, since it can lead to disease progression, organ failure, ARDS and death. Moreover, the immune system shows dysregulated activity, particularly through activated macrophages and T-helper cells and in the co-occurrent exhaustion of lymphocytes. We carried out a non-systematic literature review aimed at providing an overview of the current knowledge on the pathologic mechanisms played by the immune system and the inflammation in the genesis of SARS-CoV-2-induced lung disease. An overview on potential treatments for this harmful condition and for contrasting the "cytokine storm" has also been presented. Finally, a look at the experimented experimental vaccines against SARS-CoV-2 has been included.

Does the severity of asthma affect exercise capacity and daily physical activity?

OBJECTIVE: Exercise capacity, daily physical activity, and psychological profile are crucial aspects in the management of asthmatic patients. Whether these features are expressed in a different way in mild-moderate (MMA) and severe asthma (SA) is unknown. METHODS: In this observational cross-sectional study, patients matching the American Thoracic Society/European Respiratory Society (ATS/ERS) definition for SA underwent incremental cardiopulmonary exercise testing (CPET), full lung function testing, and an evaluation of daily step count and physical activity. Questionnaires on quality of life, general fatigue, and presence of anxiety and depression traits (Hospital Anxiety and Depression Scale - HADS) were administered. Patients were compared with a cohort of age- and gender-matched MMA patients. RESULTS: We enrolled 16 SA, 17 MMA patients, and 16 healthy subjects. Compared to MMA, SA subjects showed a median (interquartile range) reduced peak oxygen consumption during CPET (20.4 (17.2-23.3) vs. 25.6 (18.5-30.3) ml/min/kg; p = 0.019), a reduced resting lung function (FEV1% of predicted 77 (67-84) vs. 96 (84-100); p < 0.001) and a pronounced anxiety trait at HADS (9.5 (3-11.7) vs. 4.0 (2.0-7.5); p = 0.023). In addition, SA patients showed a significantly higher reduction in inspiratory capacity from rest to peak (310 (160-520) vs. 110 (-65-325) ml; p = 0.031). We found no significant differences in mean daily step count or quality of life. CONCLUSIONS: Compared to MMA, SA patients present a reduced exercise capacity and a more pronounced anxiety trait, but not worse daily physical activity or quality of life. These aspects should be considered in the clinical management and research development of SA.