COVID-19 Diagnosis in Case of Two Negative Nasopharyngeal Swabs: Association between Chest CT and Bronchoalveolar Lavage Results.

See also the editorial by Little in this issue.

Electromagnetic Navigation Bronchoscopy: Where Are We Now? Five Years of a Single-Center Experience.

INTRODUCTION: Electromagnetic navigation (ENB) is a guidance tool used in the diagnosis of solitary pulmonary nodules (SPNs) and masses. Its diagnostic yield is highly variable (38-71%) and a recent study has put in doubt the role of ENB in sampling SPNs in a real-life setting. The aim of this study is to describe the 5-year experience of our center with ENB, analyzing the population, possible confounding factors, and the diagnostic yield and accuracy of this technique. METHODS: We conducted a retrospective observational study including all consecutive patients who underwent ENB for SPNs and masses from January 2011 to December 2015. RESULTS: We included 113 patients; 79% had SPNs, 21% masses. The majority were localized in the upper and middle lobes (80%) and 61% presented a bronchus sign. 54% of the patients had a previous negative fluoroscopy-guided bronchoscopy. ENB achieved the diagnosis in 78 patients (69%) with 64 malignant and 14 were benign lesions. The diagnostic yield and accuracy of ENB were respectively 0.69 and 0.76. The only factor influencing the ability to reach a diagnosis was the presence of bronchus sign (p = 0.002). No procedural complications were reported. CONCLUSION: ENB is a safe procedure with a similar diagnostic yield in the real-life and research setting. Bronchus sign is an important factor in determining the diagnostic yield. ENB efficacy can be maximized by expertise and by a careful selection of each case.

Long-lasting consequences of coronavirus disease 19 pneumonia: a systematic review.

INTRODUCTION: Coronavirus disease 19 (COVID-19) is an infectious disease caused by the newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have plenty of data about the clinical features of the disease's acute phase, while little is known about the long-term consequences on survivors. EVIDENCE ACQUISITION: We aimed to review systematically emerging evidence about clinical and functional consequences of COVID-19 pneumonia months after hospital discharge. EVIDENCE SYNTHESIS: Current evidence supports the idea that a high proportion of COVID-19 survivors complain of symptoms months after the acute illness phase, being fatigue and reduced tolerance to physical effort the most frequently reported symptom. The strongest association for these symptoms is with the female gender, while disease severity seems less relevant. Respiratory symptoms are associated with a decline in respiratory function and, conversely, seem to be more frequent in those who experienced a more severe acute pneumonia. Current evidence highlighted a persistent motor impairment which is, again, more prevalent among those survivors who experienced a more severe acute phase of the disease. Additionally, the persistence of symptoms is a primary determinant of mental health outcome, with anxiety, depression, sleep disturbances, and post-traumatic stress symptoms being commonly reported in COVID-19 survivors. CONCLUSIONS: Current literature highlights the importance of a multidisciplinary approach to Coronavirus Disease 19 since the sequelae appear to involve different organs and systems. Given the pandemic outbreak's size, this is a critical public health issue: a better insight on this topic should inform clinical decisions about the modalities of follow-up for COVID-19 survivors.

Midterm functional sequelae and implications in rehabilitation after COVID-19: a cross-sectional study.

BACKGROUND: COVID-19 has been mainly investigated concerning the acute and subacute phase implications and management. Meanwhile, few studies focused on the midterm sequelae, which still remain largely unknown. AIM: To assess the physical performance of COVID-19 survivors at 3 to 6 months from Hospital discharge. DESIGN: A cross-sectional study focused on mid-term functional outcomes evaluation in COVID-19 survivors. SETTING: Outpatients who had been previously hospitalized due to COVID-19 from March to May 2020 at the University Hospital of Novara, Italy. POPULATION: We enrolled 204 patients, of which 60% were men, with the mean age of 57.9 years. METHODS: Patients firstly underwent the short physical performance battery test (SPPB), which is composed of a series of physical tests assessing the lower limb function and the functional status of the subjects. Subsequently, based on SPPB results, patients' cardiorespiratory fitness performance was further investigated. Patients with normal SPPB score (SPPB>10) underwent the 2-minute walking test (2MWT) whereas, in order to safely test the cardiorespiratory function, in patients with abnormal SPPB score (SPPB≤10) the 1-minute sit-to-stand test (1MSTST) was performed. It should be noted that the 1MSTST can be safely performed even by subjects with compromised walking ability. RESULTS: Overall, 66 patients (32% of our sample) showed an impaired physical performance at 3 to 6 months after hospital discharge. In particular, 29 patients presented an SPPB score ≤10, and the 1MSTST confirmed this status in the whole group (100%) compared to the reference values for age and sex. Besides, among patients with a normal SPPB score, 37 showed a lower sex- and age-matched 2MWT score. Finally, a significant association between Intensive Care Unit hospitalization or mechanical ventilation and physical impairment was observed together with a significant association between the walking ability (measured with SPPB and 2MWT) and the number of comorbidities. CONCLUSIONS: A residual physical and functional impairment was observed in COVID-19 survivors at mid-term evaluation after hospitalization. CLINICAL REHABILITATION IMPACT: Considering the current COVID-19 epidemiology, we might expect a tremendous burden of disability in the next future. Thus, an appropriate clinical rehabilitation pathway must be implemented.

Bronchoscopy during COVID-19 pandemic, ventilatory strategies and procedure measures.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has changed bronchoscopy practices worldwide. Bronchoscopy is a high-risk aerosol-generating procedure with a potential for direct SARS-CoV-2 exposure and hospital-acquired infection. Current guidelines about personal protective equipment and environment considerations represent key competencies to minimize droplets dispersion and reduce the risk of transmission. Different measures should be put in field based on setting, patient's clinical characteristics, urgency and indications of bronchoscopy. The use of this technique in SARS-CoV-2 patients is reported primarily for removal of airway plugs and for obtaining microbiological culture samples. In mechanically ventilated patients with SARS-CoV-2, bronchoscopy is commonly used to manage complications such as hemoptysis, atelectasis or lung collapse when prone positioning, physiotherapy or recruitment maneuvers have failed. Further indications are represented by assistance during percutaneous tracheostomy. Continuous positive airway pressure, non-invasive ventilation support and high flow nasal cannula oxygen are frequently used in patient affected by Coronavirus disease 2019 (COVID-19): management of patients' airways and ventilation strategies differs from bronchoscopy indications, patient's clinical status and in course or required ventilatory support. Sedation is usually administered by the pulmonologist (performing the bronchoscopy) or by the anesthetist depending on the complexity of the procedure and the level of sedation required. Lastly, elective bronchoscopy for diagnostic indications during COVID-19 pandemic should be carried on respecting rigid standards which allow to minimize potential viral transmission, independently from patient's COVID-19 status. This narrative review aims to evaluate the indications, procedural measures and ventilatory strategies of bronchoscopy performed in different settings during COVID-19 pandemic.

Comparative analysis of programmed death ligand 1 expression in paired cytologic and histologic specimens of non-small cell lung cancer.

BACKGROUND: In advanced non-small cell lung cancer (NSCLC), cytologic specimens from transbronchial needle aspiration (TBNA) or transthoracic needle aspiration are often the only cancer tissue material available for the analysis of programmed death ligand 1 (PD-L1) expression. This study was aimed at assessing the concordance of PD-L1 expression in histologic and cytologic samples and at evaluating interobserver agreement on specimens in this setting. METHODS: One hundred and thirty-eight specimens from 60 patients with NSCLC were analyzed. Histologic specimens were represented by endoscopic samples obtained with forceps (biopsies), whereas cytologic specimens were from TBNA and bronchial lavage (BL). PD-L1 expression was quantified with the immunohistochemistry (IHC)-based Ventana SP263 assay. For cytologic specimens, IHC was performed on cell block sections. Two independent pathologists who were blinded to the clinical data evaluated partial or complete membrane IHC staining. Concordance between 2 methods and between 2 pathologists was evaluated with normal and weighted Cohen's κ coefficients, overall agreement, and Bland-Altman plots. RESULTS: PD-L1 expression was quantified in 138 specimens from 60 patients. Concordance between cytologic and histologic approaches was moderate (κ = 0.56; weighted κ = 0.55). Also, concordance in the biopsy-TBNA and biopsy-BL subgroups was moderate (κ = 0.43 and κ = 0.47, respectively), whereas interobserver agreement was substantial (weighted κ = 0.72). A Bland-Altman plot showed an underestimation in PD-L1 values from cytologic samples in comparison with histologic ones. CONCLUSIONS: The results demonstrate that in the absence of available histologic specimens, PD-L1 positivity in cytologic samples could be a reliable data for the oncologist to consider immune checkpoint inhibitor therapy. However, a comparison of cytologic and histologic samples has shown an underestimation of PD-L1 values in cytologic samples.

Interferon signature in immunosuppressed patients with lower respiratory tract infections: dosage on bronchoalveolar lavage.

BACKGROUND: Interferon signature (IS) is the measure of transcripts belonging to pathways of interferon activation. Viral infections can interfere with the interferon pathway, in particular herpesvirus present in immunocompromised hosts. The aim of our study was to evaluate if herpesvirus infections in immunocompromised patients with lower respiratory tract infections (LRTI) could lead to IS alterations. METHODS: We measured IS transcription of six genes on bronchoalveolar lavage of immunocompromised patients with LRTI (IFI27, IFI44, IFIT1, ISG15, RSAD2, SIGLEC1). Patients were divided in three groups based on Epstein-Barr virus (EBV) and other herpesviruses coinfections. RESULTS: We included 56 patients, 10 without and 17 with only EBV reactivation (respectively N and E groups) and 29 with EBV and other herpesviruses (group C). IS was higher in group C (P=0.01) compared to other ones, but single gene expressions were different among groups: IFI27 was higher whereas IFIT1 and ISG15 were lower in group C (P<0.05). CONCLUSIONS: The continuous stimulation of interferon cascade by herpesviruses enhances IS. The analysis of IS in immunocompromised population is possible by limiting the use of IFI27, IFIT1, ISG15 genes. Our preliminary results seem to indicate that IS is a useful biomarker of cellular response to herpesvirus infection in immunocompromised patients.

Mild-to-moderate hemoptysis: a diagnostic and clinical challenge.

Mild-to-moderate hemoptysis is defined as the expectoration of blood or blood-streaked sputum originating from the lower respiratory tract, in volumes that do not immediately threaten the patient's life. Nevertheless, it is a very common respiratory symptom and the list of underlying respiratory or non-respiratory diseases is vast, ranging from the most worrying to more easily manageable etiologies. In this narrative review, we have analyzed the most recent recommendations inferred from the literature, in terms of diagnostic as well as therapeutic approach.

Early or delayed bronchoscopy in patients admitted to the emergency department for mild-to-moderate hemoptysis?

BACKGROUND: The correct timing for bronchoscopy in massive hemoptysis is well established, whereas in mild-to-moderate hemoptysis there still is uncertainty. The aim of our study was to evaluate if performing a fibrobronchoscopy (FBS) within 48 hours after the onset of mild-to-moderate hemoptysis was related to a higher possibility to identify the site and the cause of bleeding, compared to a delayed one. METHODS: We conducted a retrospective study over one-year period from March 2015, in which consecutive patients admitted to the emergency department underwent FBS for spontaneous mild-to-moderate hemoptysis in our medium-size teaching hospital. RESULTS: We included 69 patients. Definitive diagnosis was achieved in 52 cases (75%) combining clinical, imaging and endoscopic data (neoplastic diseases 22%, infections 20%, alveolar hemorrhage 13%). FBS was performed within 48 hours of symptoms onset in 41 patients (59%). The site of bleeding was identified in 28 cases (41%), 64% of which underwent FBS within 48 hours. Endoscopic diagnosis was reached in 45 patients (65%), 60% of which underwent FBS within 48 hours. No statistical association with localization (P=0.62) or diagnosis (P=1.00) was found with early FBS. Despite a high prevalence in our cohort of patients treated with anticoagulant or antiplatelet drugs (39%), we found no statistical association with bronchoscopy localization (P=0.12) and diagnosis (P=0.21). CONCLUSIONS: In conclusion, in case of mild to moderate hemoptysis, an early bronchoscopy in the emergency department setting does not seem to improve the possibility to find neither the cause nor the localization of the bleeding source.

Prevalence of undiagnosed chronic thromboembolic pulmonary hypertension after pulmonary embolism.

Chronic thromboembolic pulmonary hypertension is associated with adverse prognosis. Early diagnosis is important to better identify patients who would benefit from a well established therapeutic strategy. The purpose of our study was to evaluate long-term incidence of undiagnosed chronic thromboembolic pulmonary hypertension after acute pulmonary embolism and the utility of a long-term follow-up including an echocardiographic-based screening programme to early detect this disease. We evaluated retrospectively 282 patients discharged from the 'Maggiore della Carità' Hospital, Università del Piemonte Orientale, Novara, Italy, with diagnosis of acute pulmonary embolism between November 2006 and October 2009. One hundred and eleven patients underwent a clinical late echocardiographic screening programme after the acute event. Patients with suspected pulmonary hypertension based on echocardiographic evidence of systolic pulmonary artery pressure of at least 40  mmHg underwent complete work-up for chronic thromboembolic pulmonary hypertension assessment, including ventilation-perfusion lung scintigraphy and right heart catheterization. One hundred and eleven patients were included in the study. Pulmonary hypertension was suspected in 15 patients; five patients had chronic thromboembolic pulmonary hypertension confirmed by ventilation-perfusion lung scintigraphy, right heart catheterization and pulmonary angiography. Two patients with clinical class functionally advanced underwent surgical pulmonary endarterectomy and two asymptomatic patients underwent medical treatment. The prevalence of undiagnosed chronic thromboembolic pulmonary hypertension was 4.5%. Chronic thromboembolic pulmonary hypertension is a serious disease with a poor prognosis if not treated early. Surgical treatment is decisive. After surgery, the majority of patients have a substantial improvement in their functional status and in haemodynamic variables. Many patients are asymptomatic. Implementation of screening programmes may be helpful for an early diagnosis and early proper therapy.