Utility of Bronchoalveolar Lavage for the Diagnosis and Management of COVID-19 in Patients With Cancer.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) on nasopharyngeal swab (NPS), remains the most reliable and practical test to diagnose coronavirus disease 2019 (COVID-19). Current literature is sparse regarding the rates of discordance between NPS and bronchoalveolar lavage (BAL) in patients with cancer. METHODS: We conducted a retrospective cohort study of adult patients with cancer who had BAL samples tested for SARS-CoV-2 at a comprehensive cancer center. Patients without NPS PCR for SARS-CoV-2 before BAL were excluded. RESULTS: In a cohort of 345 patients, 12% and 17% tested positive for SARS-CoV-2 on NPS and BAL, respectively. There was a 6.3% NPS-/BAL+ discordance rate and a 9.5% NPS+/BAL- discordance rate. Patients with lymphoma (adjusted odds ratio [aOR] = 4.06; P = .007) and Hispanic patients (aOR = 3.76; P = .009) were more likely to have NPS-/BAL+ discordance on multivariate analysis. Among patients with NPS- /BAL- for SARS-CoV-2, an alternate infectious (23%) and a noninfectious etiology (16%) were identified in BAL. CONCLUSIONS: Our discordance rates between NPS and BAL were sufficient to recommend BAL in certain patients with cancer with a high clinical suspicion of COVID-19. BAL has value in identifying alternative etiologies of illness in patients with suspected or confirmed COVID-19.

Anticoagulation and bleeding in the cancer patient.

Cancer patients have an increased risk of bleeding compared to non-cancer patients with anticoagulant therapy. A bleeding risk assessment before initiation of anticoagulation is recommended. Currently low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs) are the mainstays of treatment for cancer-associated venous thromboembolism (VTE). Since DOACs are administered orally, they offer some convenience and ease of administration; however, LMWH may be preferred in certain cancers. Given the prevalence of anticoagulant therapies in cancer patients, clinical providers must be able to recognize potentially critical bleeding sites and modalities to reverse major hemorrhage. Reversal agents or antidotes to bleeding may be required when bleeding is persistent or life-threatening. These include vitamin K, fresh frozen plasma (FFP), protamine, prothrombin complex concentrate (PCC) or andexanet alfa, and idarucizumab. Inferior vena cava (IVC) filter insertion can be also considered in those with major bleeding. Evidence for timing and need for re-initiation of anticoagulant therapy after a major bleeding remains sparse, but a multi-disciplinary approach and shared decision-making can be implemented in the interim.

Pulmonary Function Testing in Patients with Tracheostomies: Feasibility and Technical Considerations.

PURPOSE: Pulmonary function testing (PFT) in patients with tracheostomies has been perceived as difficult to perform and clinically unreliable. We studied the feasibility, quality, repeatability and clinical significance of PFT. METHODS: Patients with tracheostomies that underwent PFT from January 1, 2010 to February 29, 2012 were identified. Clinical history and PFT data were reviewed retrospectively. RESULTS: Fifty patients (88% men) were identified. Forty-seven (94%) patients were able to perform PFT. Acceptable repeatability was obtained for FVC in 39 (83%) and for FEV1 in 41 (87%). Patients with tracheostomies showed difficulty in meeting ATS end-of-test criteria; only 9 (19%) met plateau criteria and 25 (53%) had exhalation times of greater than 6 s. Obstructive pattern was observed in 30 (64%) and restrictive pattern in 9 (19%). DLCO measurements were attempted in 43 patients and satisfactorily obtained in 34 (79%). CONCLUSIONS: PFT can be performed with reliability in patients with tracheostomies, and they are useful for detecting and classifying types of lung dysfunction.

Excessive daytime sleepiness in cancer patients.

PURPOSE: Excessive daytime sleepiness (EDS) is commonly reported in patients with cancer, and it is also a cardinal feature of central disorders of hypersomnolence. Multiple sleep latency testing (MSLT) is used for objective assessment. METHODS: A retrospective review of patients with cancer history who underwent formal sleep evaluation and MSLT from 2006 to 2019 was performed. Clinical characteristics, sleep-related history, and polysomnographic data were reviewed. RESULTS: Of 16 patients with cancer history, 9 were women (56%) and median age was 49. Cancer diagnoses included 4 central nervous system, 3 breast, 1 lymphoma, and 9 other solid malignancies, and 31% were undergoing active treatment. Comorbid conditions included depression, obstructive sleep apnea, and cancer-related fatigue. Daytime fatigue (94%), daily naps (81%), and EDS (69%) were the most common symptoms. Hypnopompic and hypnogogic hallucinations, sleep paralysis, sleep attacks, and cataplexy were present in a few. Epworth Sleepiness Scale scores were consistent with EDS in 88%, and mean sleep latency was less than 8 min in 69%. Only 31% had more than 2 sleep-onset REM periods. MSLT supported diagnoses of central disorders of hypersomnolence in 5 patients (4 narcolepsy, 1 idiopathic hypersomnia); 5 hypersomnia due to a medical disorder, psychiatric condition, or medication; and 6 with normal results. Pharmacotherapy was prescribed in 5 patients. CONCLUSIONS: EDS in patients with cancer may be multifactorial, but persistent symptoms may indicate an underlying disorder of hypersomnolence. Sleep referral and polysomnography to exclude other sleep disorders may be indicated. MSLT can help confirm the diagnosis. In those with normal MSLT, further evaluation for mood disorder should be considered.

Complications following symptom-limited thoracentesis using suction.

BACKGROUND: Thoracentesis using suction is perceived to have increased risk of complications, including pneumothorax and re-expansion pulmonary oedema (REPO). Current guidelines recommend limiting drainage to 1.5 L to avoid REPO. Our purpose was to examine the incidence of complications with symptom-limited drainage of pleural fluid using suction and identify risk factors for REPO. METHODS: A retrospective cohort study of all adult patients who underwent symptom-limited thoracentesis using suction at our institution between January 1, 2004 and August 31, 2018 was performed, and a total of 10 344 thoracenteses were included. RESULTS: Pleural fluid ≥1.5 L was removed in 19% of the procedures. Thoracentesis was stopped due to chest discomfort (39%), complete drainage of fluid (37%) and persistent cough (13%). Pneumothorax based on chest radiography was detected in 3.98%, but only 0.28% required intervention. The incidence of REPO was 0.08%. The incidence of REPO increased with Eastern Cooperative Oncology Group performance status (ECOG PS) ≥3 compounded with ≥1.5 L (0.04-0.54%; 95% CI 0.13-2.06 L). Thoracentesis in those with ipsilateral mediastinal shift did not increase complications, but less fluid was removed (p<0.01). CONCLUSIONS: Symptom-limited thoracentesis using suction is safe even with large volumes. Pneumothorax requiring intervention and REPO are both rare. There were no increased procedural complications in those with ipsilateral mediastinal shift. REPO increased with poor ECOG PS and drainage ≥1.5 L. Symptom-limited drainage using suction without pleural manometry is safe.

Pulmonary Impairment after Respiratory Viral Infections Is Associated with High Mortality in Allogeneic Hematopoietic Cell Transplant Recipients.

Pulmonary impairment predicts increased mortality in many settings, and respiratory viral infection (RVI) causes considerable morbidity and mortality in allogeneic hematopoietic cell transplant recipients (allo-HCT). We hypothesized that pulmonary impairment after RVI, defined as a decline of forced expiratory volume in 1 second values by ≥10%, may identify allo-HCT recipients at high risk for mortality. We studied all allo-HCT recipients at our institution who had RVI with respiratory syncytial virus, parainfluenza virus, or influenza from 2004 to 2013 and had pre-RVI and post-RVI pulmonary function tests. We used competing risk regression models to identify risk factors for 2-year nonrelapse mortality (NRM) as the primary outcome after RVI and relapse-related mortality as a competing risk. From 223 eligible patients, pulmonary impairment after RVI was associated with over a 3-fold increase in 2-year NRM (pulmonary impairment, 25.3%; no impairment, 7.4%; univariate subhazard ratio [SHR], 3.9; 95% confidence interval [CI], 1.9 to 8.1; P < .001). After adjusting for age and systemic steroid use, pulmonary impairment after RVI was still associated with increased 2-year NRM (SHR, 3.3 [95% CI, 1.6 to 6.9]; P = .002). After adjustment for race and graft-versus-host disease (GVHD) prophylaxis, chronic GVHD at the time of RVI (odds ratio [OR], 2.8 [95% CI, 1.4 to 5.4]; p = .003) and lymphopenia (OR, 2.2 [95% CI, 1.1 to 4.2]; P = .02) were associated with increased odds of pulmonary impairment, whereas use of nonmyeloablative conditioning was associated with reduced odds of pulmonary impairment (OR, .4 [95% CI, .2 to .8]; P = .006). In allo-HCT recipients with RVIs, pulmonary impairment after RVI is associated with high NRM at 2years.

Refinement of estimates of mortality risk using the Radiologic Severity Index in hematologic malignancy patients with respiratory syncytial virus infection.

BACKGROUND: Immunocompromised hematologic malignancy (HM) patients experience high mortality after respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI). We measured radiologic severity to determine whether it could improve the performance of 60-day mortality models based only upon immunodeficiency severity. METHODS: We studied 155 HM patients, including 84 hematopoietic cell transplant recipients, who developed RSV LRTI from 2001 to 2013. We measured immunodeficiency using lymphopenia (lymphocyte count <200 cells/mm3 ), Immunodeficiency Severity Index (ISI), and Severe Immunodeficiency (SID) criteria. Radiologic severity was measured by the Radiologic Severity Index (RSI, range 0-72) at time of LRTI (baseline-RSI) and peak severity (peak-RSI). Delta-RSI was defined as the difference between baseline-RSI and peak-RSI. We used logistic regression models to measure the association of immunodeficiency and RSI with 60-day all-cause mortality, and measured model discrimination using areas under the receiver-operating characteristics curves, calibration using Brier scores, and explained variance using pseudo-R2 values. RESULTS: Forty-one patients died within 60 days of RSV LRTI. Severe immunodeficiency was associated with higher mortality. Peak-RSI (odds ratio [OR] 1.06/point, 95% confidence interval [CI] 1.04-1.08), and delta-RSI (OR 1.07/point, 95% CI 1.05-1.10) were associated with 60-day mortality after RSV LRTI, but not baseline-RSI. Addition of peak-RSI or delta-RSI to baseline immunodeficiency improved the discrimination, calibration, and explained variance (P < 0.001) of 60-day mortality models. CONCLUSIONS: Although baseline immunodeficiency in HM patients helps predict 60-day mortality after RSV LRTI, mortality risk estimates can be further refined by also measuring LRTI progression using RSI. RSI is well-suited as a marker of LRTI severity in RSV infection.

Risk factors for mortality after respiratory syncytial virus lower respiratory tract infection in adults with hematologic malignancies.

BACKGROUND: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is associated with high mortality in patients with hematologic malignancies (HM). We sought to determine whether allogeneic hematopoietic cell transplant (allo-HCT) recipients would be at higher risk for 60-day mortality. METHODS: We examined a retrospective cohort of adults with HM with or without HCT treated for RSV LRTI (n = 154) at our institution from 1996-2013. We defined possible RSV LRTI as RSV detected only in the upper respiratory tract with new radiologic infiltrates and proven RSV LRTI as RSV detected in BAL fluid with new radiologic infiltrates. Immunodeficiency Scoring Index (ISI) and Severe Immunodeficiency (SID) criteria were calculated for HCT recipients. Multivariable logistic regression analyses were performed to identify independent risk factors associated with 60-day all-cause mortality. RESULTS: Mortality was high in HM patients (25%), but there was no difference between those without HCT, autologous or allo-HCT recipients in logistic regression models. Separate multivariate models showed that at RSV diagnosis, neutropenia (OR 8.3, 95% CI 2.8-24.2, P = 0.005) and lymphopenia (OR 3.7, 95% CI 1.7-8.2, P = 0.001) were associated with 60-day mortality. Proven LRTI was associated with higher 60-day mortality (neutropenia model: OR 4.7, 95%CI 1.7-13.5; lymphopenia model: OR 3.3, 95% CI 1.2-8.8), and higher ICU admission. In HCT recipients, high ISI and very severe immunodeficiency by SID criteria were associated with higher 60-day all-cause mortality. CONCLUSIONS: Mortality is similarly high among HM patients without HCT and HCT recipients. High-grade immunodeficiency and detection of RSV from BAL fluid are associated with higher 60-day mortality.

Sleep-related breathing disorders in patients with tumors in the head and neck region.

BACKGROUND: Sleep disturbance is a prominent complaint of cancer patients. Most studies have focused on insomnia and cancer-related fatigue. Obstructive sleep apnea (OSA) has been reported in small studies and case reports. METHODS: In a retrospective review of patients who underwent formal sleep evaluation and polysomnography (PSG) from 2006 to 2011, 56 patients with tumors in the head and neck region were identified. Clinical characteristics, sleep-related history, and PSG data were reviewed. RESULTS: Most patients had active cancer (80%), and the majority had squamous pathology (68%). Prominent symptoms included daytime fatigue (93%), daytime sleepiness (89%), and snoring (82%). Comorbid conditions primarily included hypertension (46%) and hypothyroidism (34%). Significant sleep-related breathing disorder was noted in 93% of patients, and 84% met clinical criteria for OSA. A male predominance (77%) was noted, and patients were not obese (body mass index <30 kg/m(2) in 52%). The majority of patients (79%) underwent radiation prior to sleep study, of which 88% had OSA, and in the group without prior radiation, 67% had OSA. Adherence to positive airway pressure (PAP) therapy was slightly better when compared with the general population. A subset of patients with persistent hypoxia despite advanced forms of PAP required tracheostomy. Multivariate analysis revealed that patients with active disease and radiation prior to PSG were more likely to have OSA. CONCLUSION: Sleep-related breathing disorder was common in patients with tumors in the head and neck region referred for evaluation of sleep disruption, and most met clinical criteria for OSA. Daytime fatigue and sleepiness were the most common complaints. OSA was prevalent in male patients, and most with OSA were not obese. Architectural distortion from the malignancy and/or treatment may predispose these patients to OSA by altering anatomic and neural factors. A heightened clinical suspicion for sleep-related breathing disorder and referral to a sleep specialist would be beneficial for patients with these complaints.

GRAvity- versus Wall suction-drIven large volume Thoracentesis: a rAndomized controlled Study (GRAWITAS study).

BACKGROUND: Prior studies found no differences in procedural chest discomfort for patients undergoing manual syringe aspiration or drainage with gravity after thoracentesis. However, whether gravity drainage could protect against chest pain due to the larger negative pressure gradient generated by wall suction has not been investigated. RESEARCH QUESTION: Does wall suction drainage result in more chest discomfort compared to gravity drainage in patients undergoing large volume thoracentesis? STUDY DESIGN AND METHODS: In this multicenter, single-blinded, randomized controlled trial, patients with large free-flowing effusions of ≥500 mL were assigned to wall suction or gravity drainage in a 1:1 ratio. Wall suction was performed with suction system attached to the suction tubing and with vacuum pressure adjusted to full vacuum. Gravity drainage was performed with a drainage bag placed 100 cm below the catheter insertion site and connected via straight tubing. Patients rated chest discomfort on a 100-mm visual analog scale before, during, and after drainage. The primary outcome was postprocedural chest discomfort at 5 minutes. Secondary outcomes included measures of post procedure chest discomfort, breathlessness, procedure time, volume of fluid drained and complication rates. RESULTS: Of the 228 patients initially randomized, 221 were included in the final analysis. The primary outcome of procedural chest discomfort did not differ significantly between the groups (p = 0.08), nor did the secondary outcomes of postprocedural discomfort and dyspnea. Similar volumes were drained in both groups, but the procedure duration was longer in the gravity arm by approximately 3 minutes. No differences in rate of pneumothorax or re-expansion pulmonary edema were noted between the two groups. INTERPRETATION: Thoracentesis via wall suction and gravity drainage results in similar levels of procedural discomfort and dyspnea improvement.

The Impact of Immunotherapy on Sleep and Circadian Rhythms in Patients with Cancer.

Immunotherapy has revolutionized treatments for both early and advanced cancers, and as their role evolves, their impact on sleep and circadian rhythms continues to unfold. The recognition, evaluation, and treatment of sleep and circadian rhythm disturbance leads to improved symptom management, quality of life and treatment outcomes. An intricate complex relationship exists in the microenvironment with immunity, sleep and the tumor, and these may further vary based on the cancer, addition of standard chemotherapy, and pre-existing patient factors. Sleep and circadian rhythms may offer tools to better utilize immunotherapy in the care of cancer patients, leading to better treatment outcome, reduced symptom burden, and increased quality of life.

Risk Factors for Bronchiolitis Obliterans Syndrome after Initial Detection of Pulmonary Impairment after Hematopoietic Cell Transplantation.

Pulmonary chronic graft-versus-host-disease (cGVHD), or bronchiolitis obliterans syndrome (BOS), is a highly morbid complication of hematopoietic cell transplantation (HCT). The clinical significance of a single instance of pulmonary decline not meeting the criteria for BOS is unclear. We conducted a retrospective analysis in a cohort of patients who had an initial post-HCT decline in the absolute value of forced expiratory volume in 1 second (FEV1) of ≥10% or mid-expiratory flow rate of ≥25% but not meeting the criteria for BOS (pre-BOS). We examined the impact of clinical variables in patients with pre-BOS on the risk for subsequent BOS. Pre-BOS developed in 1325 of 3170 patients (42%), of whom 72 (5%) later developed BOS. Eighty-four patients developed BOS without detection of pre-BOS by routine screening. Among patients with pre-BOS, after adjusting for other significant variables, airflow obstruction (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.1 to 3.7; P = .02), percent-predicted FEV1 on decline (HR, .98; 95% CI, .97 to 1.0; P = .02), active cGVHD (HR, 7.7; 95% CI, 3.1 to 19.3; P < .001), peripheral blood stem cell source (HR, 3.8; 95% CI, 1.7 to 8.6; P = .001), and myeloablative conditioning (HR, 2.0; 95% CI, 1.1 to 3.5; P = .02) were associated with subsequent BOS. The absence of airflow obstruction and cGVHD had a negative predictive value of 100% at 6 months for subsequent BOS, but the positive predictive value of both factors was low (cGVHD, 3%; any obstruction, 4%; combined, 6%). Several clinical factors at the time of pre-BOS, particularly active cGVHD and airflow obstruction, increase the risk for subsequent BOS. These factors merit consideration to be included in screening practices to improve the detection of BOS, with the caveat that the predictive utility of these factors is limited by the overall low incidence of BOS among patients with pre-BOS.

Interstitial lung abnormalities after hospitalization for COVID-19 in patients with cancer: A prospective cohort study.

INTRODUCTION: Survivors of SARS-CoV-2 pneumonia often develop persistent respiratory symptom and interstitial lung abnormalities (ILAs) after infection. Risk factors for ILA development and duration of ILA persistence after SARS-CoV-2 infection are not well described in immunocompromised hosts, such as cancer patients. METHODS: We conducted a prospective cohort study of 95 patients at a major cancer center and 45 patients at a tertiary referral center. We collected clinical and radiographic data during the index hospitalization for COVID-19 pneumonia and measured pneumonia severity using a semi-quantitative radiographic score, the Radiologic Severity Index (RSI). Patients were evaluated in post-COVID-19 clinics at 3 and 6 months after discharge and underwent comprehensive pulmonary evaluations (symptom assessment, chest computed tomography, pulmonary function tests, 6-min walk test). The association of clinical and radiological factors with ILAs at 3 and 6 months post-discharge was measured using univariable and multivariable logistic regression. RESULTS: Sixty-six (70%) patients of cancer cohort had ILAs at 3 months, of whom 39 had persistent respiratory symptoms. Twenty-four (26%) patients had persistent ILA at 6 months after hospital discharge. In adjusted models, higher peak RSI at admission was associated with ILAs at 3 (OR 1.5 per 5-point increase, 95% CI 1.1-1.9) and 6 months (OR 1.3 per 5-point increase, 95% CI 1.1-1.6) post-discharge. Fibrotic ILAs (reticulation, traction bronchiectasis, and architectural distortion) were more common at 6 months post-discharge. CONCLUSIONS: Post-COVID-19 ILAs are common in cancer patients 3 months after hospital discharge, and peak RSI and older age are strong predictors of persistent ILAs.

A Nasal Inflammatory Cytokine Signature Is Associated with Early Graft-versus-Host Disease of the Lung after Allogeneic Hematopoietic Cell Transplantation: Proof of Concept.

Respiratory inflammation in bronchiolitis obliterans syndrome (BOS) after hematopoietic cell transplantation (HCT) is poorly understood. Clinical criteria for early-stage BOS (stage 0p) often capture HCT recipients without BOS. Measuring respiratory tract inflammation may help identify BOS, particularly early BOS. We conducted a prospective observational study in HCT recipients with new-onset BOS (n = 14), BOS stage 0p (n = 10), and recipients without lung impairment with (n = 3) or without (n = 8) chronic graft-versus-host disease and measured nasal inflammation using nasosorption at enrollment and then every 3 mo for 1 y. We divided BOS stage 0p into impairment that did not return to baseline values (preBOS, n = 6), or transient impairment (n = 4). We tested eluted nasal mucosal lining fluid from nasosorption matrices for inflammatory chemokines and cytokines using multiplex magnetic bead immunoassays. We analyzed between-group differences using the Kruskal-Wallis method, adjusting for multiple comparisons. We found increased nasal inflammation in preBOS and therefore directly compared patients with preBOS to those with transient impairment, as this would be of greatest diagnostic relevance. After adjusting for multiple corrections, we found significant increases in growth factors (FGF2, TGF-α, GM-CSF, VEGF), macrophage activation (CCL4, TNF-α, IL-6), neutrophil activation (CXCL2, IL-8), T cell activation (CD40 ligand, IL-2, IL-12p70, IL-15), type 2 inflammation (eotaxin, IL-4, IL-13), type 17 inflammation (IL-17A), dendritic maturation (FLT3 ligand, IL-7), and counterregulatory molecules (PD-L1, IL-1 receptor antagonist, IL-10) in preBOS patients compared to transient impairment. These differences waned over time. In conclusion, a transient multifaceted nasal inflammatory response is associated with preBOS. Our findings require validation in larger longitudinal cohorts.

Consolidative opacity in a patient with acute leukemia.

27 year old man with newly diagnosed acute myeloid leukemia presents with new parenchymal consolidation. Although biopsy was precluded, diagnostic studies support myeloid sarcoma. Resolution of consolidation occurred with hematopoietic stem cell transplantation.