Application of Global Lung Function Initiative Global Spirometry Reference Equations across a Large, Multicenter Pulmonary Function Lab Population.

Rationale: Global Lung Function Initiative (GLI) Global spirometry reference equations were recently derived to offer a "race-neutral" interpretation option. The impact of transitioning from the race-specific GLI-2012 to the GLI Global reference equations is unknown. Objectives: Describe the direction and magnitude of changes in predicted lung function measurements in a population of diverse race and ethnicity using GLI Global in place of GLI-2012 reference equations. Methods: In this multicenter cross-sectional study using a large pulmonary function laboratory database, 109,447 spirometry tests were reanalyzed using GLI Global reference equations and compared with the existing GLI-2012 standard, stratified by self-reported race and ethnicity. Measurements and Main Results: Mean FEV1 and FVC percent predicted increased in the White and Northeast Asian groups and decreased in the Black, Southeast Asian, and mixed/other race groups. The prevalence of obstruction increased by 9.7% in the White group, and prevalences of possible restriction increased by 51.1% and 37.1% in the Black and Southeast Asian groups, respectively. Using GLI Global in a population with equal representation of all five race and ethnicity groups altered the interpretation category for 10.2% of spirometry tests. Subjects who self-identified as Black were the only group with a relative increase in the frequency of abnormal spirometry test results (32.9%). Conclusions: The use of GLI Global reference equations will significantly impact spirometry interpretation. Although GLI Global offers an innovative approach to transition from race-specific reference equations, it is important to recognize the continued need to place these data within an appropriate clinical context.

The Perils and Pitfalls of Esophageal Dysmotility in Idiopathic Pulmonary Fibrosis.

INTRODUCTION: Gastroesophageal reflux plays a significant role in idiopathic pulmonary fibrosis (IPF). Given the morbidity and mortality associated with IPF, understanding the mechanisms responsible for reflux is essential if patients are to receive optimal treatment and management, especially given the lack of clear benefit of antireflux therapies. Our aim was to understand the inter-relationships between esophageal motility, lung mechanics and reflux (particularly proximal reflux-a prerequisite of aspiration), and pulmonary function in patients with IPF. METHODS: We prospectively recruited 35 patients with IPF (aged 53-75 years; 27 men) who underwent high-resolution impedance manometry and 24-hour pH-impedance, together with pulmonary function assessment. RESULTS: Twenty-two patients (63%) exhibited dysmotility, 16 (73%) exhibited ineffective esophageal motility (IEM), and 6 (27%) exhibited esophagogastric junction outflow obstruction. Patients with IEM had more severe pulmonary disease (% forced vital capacity: P = 0.032) and more proximal reflux (P = 0.074) than patients with normal motility. In patients with IEM, intrathoracic pressure inversely correlated with the number of proximal events (r = -0.429; P = 0.098). Surprisingly, inspiratory lower esophageal sphincter pressure (LESP) positively correlated with the percentage of reflux events reaching the proximal esophagus (r = 0.583; P = 0.018), whereas in patients with normal motility, it inversely correlated with the bolus exposure time (r = -0.478; P = 0.098) and number of proximal events (r = -0.542; P = 0.056). % forced vital capacity in patients with IEM inversely correlated with the percentage of reflux events reaching the proximal esophagus (r = -0.520; P = 0.039) and inspiratory LESP (r = -0.477; P = 0.062) and positively correlated with intrathoracic pressure (r = 0.633; P = 0.008). DISCUSSION: We have shown that pulmonary function is worse in patients with IEM which is associated with more proximal reflux events, the latter correlating with lower intrathoracic pressures and higher LESPs.

Association between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Lung Cancer.

OBJECTIVES: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are the most commonly prescribed antihypertensives, with prior studies identifying a possible association between long-term use and increased rates of lung cancer. This study evaluated this potential association in a large population using propensity matching. METHODS: This was a population-based cohort study in a large healthcare system in three regions of the United States. Pairwise propensity score matching was performed using demographics and comorbidities. All of the adult patients in the healthcare system from January 1, 2000 to April 30, 2018 with at least 1 year of follow-up were included. RESULTS: In total, 3,253,811 patients with a median age of 59 (range 18-103) years were included. The ACEI group had a higher freedom from lung cancer versus controls at 15 years (98.47%, 95% confidence interval [CI] 98.41-98.54) versus 98.26%, (95% CI 98.20-98.33), whereas ARBs had similar rates versus controls at all time points. For patients diagnosed as having lung cancer, median all-cause survival was significantly higher in the ACEI (34.7 months, 95% CI 32.8-36.6) and ARB (30.9 months, 95% CI 28.1-33.8) groups than the control group (20.6 months, 95% CI 20.1-21.1). CONCLUSIONS: This study showed lower rates of lung cancer with ACEI use and no difference in risk with ARBs. In addition, use of these medications was found to be associated with increased survival in those diagnosed as having lung cancer. This study supports the continued use of these medications without concern for increasing the risk of lung cancer.

Interstitial Lung Disease in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Patients: Comparison With Idiopathic Pulmonary Fibrosis.

BACKGROUND/OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may involve the kidney, respiratory tract, skin, or central and peripheral nervous system. Reports of interstitial lung disease (ILD) in AAV (AAV-ILD) have been increasing. METHODS: We reviewed the medical records of all patients with AAV-ILD between January 1, 2007, and December 31, 2017, and compared their pulmonary involvement to patients with idiopathic pulmonary fibrosis (IPF). RESULTS: We identified 24 patients with AAV-ILD: 14 with microscopic polyangiitis, 8 with granulomatosis with polyangiitis, and 2 with eosinophilic granulomatosis with polyangiitis. Perinuclear or myeloperoxidase ANCA was present in 16 cases (66.7%), whereas cytoplasmic or proteinase 3 ANCA was positive in 8 (33.3%). Usual interstitial pneumonia (UIP) was seen in 11 (45.8%), probable UIP in 1 (4.2%), indeterminate UIP in 2 (8.3%), and an alternate diagnosis in 10 (41.7%), and was further characterized as chronic hypersensitivity pneumonitis-like pattern seen in 6 (25%), nonspecific interstitial pneumonia-like pattern in 3 (12.5%), and cryptogenic organizing pneumonia-like pattern in 1 (4.2%). Forced vital capacity and diffusing capacity declined over time in patients with AAV-ILD. When compared with the IPF cohort, patients with AAV-ILD had intermediate survival and speed of lung function decline (3-year survival in AAV-ILD group was 94% vs 69% in IPF). CONCLUSIONS: Antineutrophil cytoplasmic antibody-associated vasculitis ILD is a progressive and potentially fatal condition. Although most cases in the literature are associated with p-ANCA and positive myeloperoxidase, we found that a third of patients had c-ANCA or granulomatosis with polyangiitis. Our cohort adds experience in this rare manifestation of AAV.

Unilateral Versus Bilateral Lung Transplantation: Do Different Esophageal Risk Factors Predict Chronic Allograft Failure?

GOALS: To assess the effect of unilateral versus bilateral lung transplantation (LTx) on esophageal motility and gastroesophageal reflux, and the association with the development of obstructive chronic lung allograft dysfunction (o-CLAD). BACKGROUND: We have shown that esophagogastric junction outflow obstruction, incomplete bolus transit, and proximal reflux are all independent risk factors for the development of chronic allograft failure. However, it remains unclear whether these factors are influenced by the type of surgery and how this relates to allograft failure. STUDY: Patients post-LTx (n=48, 24 female; aged 20 to 73 y) completed high-resolution impedance manometry and 24-hour pH/impedance. RESULTS: Patients who had undergone unilateral LTx were more likely to exhibit esophagogastric junction outflow obstruction (47% vs. 18%; P=0.046) and less likely to exhibit hypocontractility (0% vs. 21%; P=0.058) than those who had undergone bilateral LTx. Although the proportion of patients exhibiting gastroesophageal reflux was no different between groups (33% vs. 39%; P=0.505), those undergoing bilateral LTx were more likely to exhibit proximal reflux (8% vs. 37%; P=0.067). Univariate Cox proportion hazards regression analysis did not show a difference between unilateral versus bilateral LTx in the development of o-CLAD (hazard ratio=1.17; 95% confidence interval, 0.48-2.85; P=0.723). CONCLUSION: The type of LTx performed seems to lead to different risk factors for the development of o-CLAD. Physicians should be aware of these differences, as they may need to be taken into account when managing patient's post-LTx.

A novel semiquantitative assessment of right ventricular systolic function with a modified subcostal echocardiographic view.

OBJECTIVES: The tricuspid annular plane systolic excursion (TAPSE) is a validated measure of right ventricular function; however, the apical echocardiographic window varies and has limitations in intensive care unit (ICU) patients receiving mechanical ventilation or those with underlying disease and air entrapment. We aimed to evaluate the subcostal echocardiographic assessment of tricuspid annular kick (SEATAK) as an alternative to TAPSE in critically ill patients. METHODS: To measure SEATAK, we obtained the subcostal inferior vena cava view and used M-mode to measure excursion of the tricuspid annulus (kick). Analysis was performed with JMP for Bland-Altman and Spearman correlations. RESULTS: We evaluated 45 patients, 26 (57.8%) of whom were women, with a mean age of 60.8 years. We were not able to obtain the apical view to measure TAPSE in 8.9% of the patients. In contrast, SEATAK was measured in all patients. The mean SEATAK and TAPSE were 1.62 cm and 1.93 cm, respectively, with a mean pairwise difference of -0.26 cm (95% CI: -0.19 to -0.35), with the SEATAK value being lower than TAPSE. The overall correlation was strong and significant (ρ = .86, P=.03). The graphical correlation was maintained between TAPSE and SEATAK and the degree of RVF. CONCLUSION: In patients presenting with RVF in the ICU (or in situations where the apical echocardiographic view is suboptimal for tricuspid annular assessment), SEATAK can be an alternative to TAPSE. Further research is needed to validate and determine the sensitivity and specificity of SEATAK for RVF prognostication.

Willis-Ekbom disease is not associated with poor cardiovascular health in adults.

BACKGROUND: Willis-Ekbom disease (WED), also called restless legs syndrome (RLS), is a neurologic sensorimotor disease that may be associated with cardiovascular disease. Given high morbidity and mortality rates of cardiovascular disease worldwide, we assessed the relation between WED/RLS and cardiovascular health risks in a native South American population. We prospectively analyzed data from The Atahualpa Project of Ecuadorian adults aged 40 years and older. Physicians interviewed consented persons on the health behavior and health factors of the American Heart Association (AHA) for ideal cardiovascular health in adults and underwent fasting laboratory blood collection and blood pressure evaluation. Certified neurologists conducted face-to-face interviews using the International Restless Legs Syndrome Study Group (IRLSSG) field instrument. Persons testing positive for WED/RLS and age-and sex-matched controls underwent confirmatory physical examinations conducted by a neurologist and a sleep specialist to whom IRLSSG designation was blinded. FINDINGS: Of 665 persons, 94 (14 %) tested positive in IRLSSG; 40 (6 %) had a diagnosis of WED/RLS after neurologic examination and interview. Patients with WED/RLS were younger (53.5 vs 59.9 years, P = .001), without significant differences in sex ratios. Among AHA risk factors, only obesity was significantly more prevalent among patients with WED/RLS (42.5 % vs 23.5 %, P = .01). However, after adjustment for confounders, body mass index was not significantly associated with WED/RLS. CONCLUSIONS: In adult Amerindians, although obesity and body mass index were associated with WED/RLS on univariate analyses, the association was not present after adjustment for confounders. No other significant associations were found between WED/RLS and AHA cardiovascular metrics.

Effect of prolonged therapeutic hypothermia on intracranial pressure, organ function, and hospital outcomes among patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Global cerebral edema (GCE) with subsequent refractory intracranial hypertension complicates some cases of aneurysmal subarachnoid hemorrhage (aSAH), and typically is associated with poorer outcome. Treatment options for refractory intracranial pressure (ICP) cases are limited to decompressive hemicraniectomy (DHC) and targeted temperature management (TTM) with induced hypothermia (32-34 °C). No outcomes comparison between patients treated with either or both forms of refractory ICP therapy exists, and data on the effect of prolonged hypothermia on ICP and organ function among patients with aSAH are limited. METHODS: This is a retrospective study of aSAH patients who underwent DHC and/or prolonged hypothermia (greater than 48 h) for refractory ICP (i.e., ICP >20 mmHg after osmotherapy) in the intensive care unit of a single, tertiary-care academic center. RESULTS: Nineteen individuals with aSAH underwent TTM with or without DHC; sixteen patients underwent DHC alone. The patients in TTM group were younger (median age 44 years) than the DHC without TTM population (median age 60 years). TTM was started on median day 2 with a median duration of 7 days. There were no significant group differences in survival to discharge (59 % vs. 69 %) or in the mean modified Rankin score on follow-up (3.6 vs. 3.7), despite the TTM group having longer hospital length of stay (24 vs. 19 days, p = 0.03), longer duration of mechanical ventilation (20 vs. 9 days, p = 0.04), a higher cumulative fluid balance (12.8 vs. 5.1 L, p = 0.01), and higher APACHEII scores. The median maximal ICP decreased from 23.5 to 21 mmHg within 24 h of hypothermia initiation. There were no significant differences in other markers of end-organ function (respiratory, hematologic, renal, liver, and cardiac), infection rate, or adverse events between groups. CONCLUSIONS: Use of prolonged TTM among aSAH patients with GCE and refractory ICP elevations is associated with a longer duration of mechanical ventilation but is not different in terms of neurological outcomes measured by modified Rankin score or organ function outcomes compared to patients who received DHC alone.

Screening for connective tissue disease in pulmonary arterial hypertension.

OBJECTIVES: To evaluate the utility of anti-nuclear antibody (ANA) levels in distinguishing the cause of pulmonary arterial hypertension as idiopathic (IPAH) or connective tissue disease related (CTD-PAH). METHODS: We retrospectively identified patients with IPAH or CTD-PAH seen between 2010 and 2012 at our institution. Medical records were reviewed for demographic and clinical data and laboratory values. RESULTS: Of 115 patients identified, 65 (56%) had IPAH and 50 (44%) had CTD-PAH. The mean age was 59 years and most of the patients (76%) were women. Most patients (64%) were in World Health Organization functional class III or IV. Compared with the IPAH group, the CTD-PAH group had significantly increased B-type natriuretic peptide levels (635 vs 325 pg/mL; P = 0.02) and decreased pulmonary vascular resistance (6 vs 9 WU; P = 0.04). The median ANA level was significantly higher in the CTD-PAH group than the IPAH group (7 vs 0 U; P < 0.001). The area under the receiver operating characteristic curve for a positive ANA to predict CTD-PAH was 0.91 (P < 0.001). A cutoff of 5 U for predicting ANA provided an optimal specificity of 94% and a sensitivity of 70%. The resulting likelihood ratio using the same cutoff was 12 (P < 0.001), or a positive predictive value of 91% with a negative predictive value of 79%. CONCLUSIONS: In this selected cohort of patients, a quantitative ANA value >5 U may be useful in distinguishing CTD-PAH from IPAH, but a lower level does not confidently exclude CTD-PAH.

The impact of lung transplantation on esophageal motility and inter-relationships with reflux and lung mechanics in patients with restrictive and obstructive respiratory disease.

BACKGROUND: For many patients with lung disease the only proven intervention to improve survival and quality of life is lung transplantation (LTx). Esophageal dysmotility and gastroesophageal reflux (GER) are common in patients with respiratory disease, and often associate with worse prognosis following LTx. Which, if any patients, should be excluded from LTx based on esophageal concerns remains unclear. Our aim was to understand the effect of LTx on esophageal motility diagnosis and examine how this and the other physiological and mechanical factors relate to GER and clearance of boluses swallowed. METHODS: We prospectively recruited 62 patients with restrictive (RLD) and obstructive (OLD) lung disease (aged 33-75 years; 42 men) who underwent high resolution impedance manometry and 24-h pH-impedance before and after LTx. KEY RESULTS: RLD patients with normal motility were more likely to remain normal (p = 0.02), or if having abnormal motility to change to normal (p = 0.07) post-LTx than OLD patients. Esophageal length (EL) was greater in OLD than RLD patients' pre-LTx (p < 0.001), reducing only in OLD patients' post-LTx (p = 0.02). Reduced EL post-LTx associated with greater contractile reserve (r = 0.735; p = 0.01) and increased likelihood of motility normalization (p = 0.10). Clearance of reflux improved (p = 0.01) and associated with increased mean nocturnal baseline impedance (p < 0.001) in RLD but not OLD. Peristaltic breaks and thoraco-abdominal pressure gradient impact both esophageal clearance of reflux and boluses swallowed (p < 0.05). CONCLUSIONS AND INFERENCES: RLD patients are more likely to show improvement in esophageal motility than OLD patients post-LTx. However, the effect on GER is more difficult to predict and requires other GI, anatomical and pulmonary factors to be taken into consideration.

Risk of 30-Day All-Cause Readmission in Interstitial Lung Disease Patients after COVID-19: National-Level Data.

Rationale: Hospital readmission within 30 days poses challenges for healthcare providers, policymakers, and patients because of its impact on care quality, costs, and outcomes. Patients with interstitial lung disease (ILD) are particularly affected by readmission, which is associated with increased morbidity and mortality and reduced quality of life. Because small sample sizes have hindered previous studies, this study seeks to address this gap in knowledge by examining a large-scale dataset. Objective: To determine the rate and probability of 30-day all-cause readmission and secondary outcomes in patients with coronavirus disease (COVID-19) or ILD admitted to the hospital. Methods: This study is a nested cohort study that used the PearlDiver patient records database. Adult patients (age ⩾18 yr) who were admitted to hospitals in 28 states in the United States with COVID-19 or ILD diagnoses were included. We defined and analyzed two separate cohorts in this study. The first cohort consisted of patients with COVID-19 and was later divided into two groups with or without a history of ILD. The second cohort consisted of patients with ILD and was later divided into groups with COVID-19 or with a non-COVID-19 pneumonia diagnosis at admission. We also studied two other subcohorts of patients with and without idiopathic pulmonary fibrosis within the second cohort. Propensity score matching was employed to match confounders between groups. The Kaplan-Meier log rank test was applied to compare the probabilities of outcomes. Results: We assessed the data of 2,286,775 patients with COVID-19 and 118,892 patients with ILD. We found that patients with COVID-19 with preexisting ILD had an odds ratio of 1.6 for 30-day all-cause readmission. Similarly, an odds ratio of 2.42 in readmission rates was observed among hospitalized individuals with ILD who contracted COVID-19 compared with those who were hospitalized for non-COVID-19 pneumonia. Our study also found a significantly higher probability of intensive care admission among patients in both cohorts. Conclusions: Patients with ILD face heightened rates of hospital readmissions, particularly when ILD is combined with COVID-19, resulting in adverse outcomes such as decreased quality of life and increased healthcare expenses. It is imperative to prioritize preventive measures against COVID-19 and establish effective postdischarge care strategies for patients with ILD.

The influence of prehospital systemic corticosteroid use on development of acute respiratory distress syndrome and hospital outcomes.

OBJECTIVE: The role of systemic corticosteroids in pathophysiology and treatment of acute respiratory distress syndrome is controversial. Use of prehospital systemic corticosteroid therapy may prevent the development of acute respiratory distress syndrome and improve hospital outcomes. DESIGN: This is a preplanned retrospective subgroup analysis of the prospectively identified cohort from a trial by the U.S. Critical Illness and Injury Trials Group designed to validate the Lung Injury Prediction Score. SETTING: Twenty-two acute care hospitals. PATIENTS: : Five thousand eighty-nine patients with at least one risk factor for acute respiratory distress syndrome at the time of hospitalization. INTERVENTION: Propensity-based analysis of previously recorded data. MEASUREMENTS AND MAIN RESULTS: Three hundred sixty-four patients were on systemic corticosteroids. Prevalence of acute respiratory distress syndrome was 7.7% and 6.9% (odds ratio, 1.1 [95% CI, 0.8-1.7]; p = 0.54) for patients on systemic corticosteroid and not on systemic corticosteroids, respectively. A propensity for being on systemic corticosteroids was derived through logistic regression by using all available covariates. Subsequently, 354 patients (97%) on systemic corticosteroids were matched to 1,093 not on systemic corticosteroids by their propensity score for a total of 1,447 patients in the matched set. Adjusted risk for acute respiratory distress syndrome (odds ratio, 0.96 [95% CI, 0.54-1.38]), invasive ventilation (odds ratio, 0.84 [95% CI, 0.62-1.12]), and in-hospital mortality (odds ratio, 0.97 [95% CI, 0.63-1.49]) was then calculated from the propensity-matched sample using conditional logistic regression model. No significant associations were present. CONCLUSIONS: Prehospital use of systemic corticosteroids neither decreased the development of acute respiratory distress syndrome among patients hospitalized with at one least risk factor, nor affected the need for mechanical ventilation or hospital mortality.

Blood transfusion is an important predictor of hospital mortality among patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Red blood cell (RBC) transfusion after aneurysmal subarachnoid hemorrhage (aSAH) has been associated with increased mortality but prior studies have not adequately adjusted for transfusion-indication bias. METHODS: This is a retrospective study of consecutive aSAH patients admitted to the intensive care units of two academic medical centers over a 7-year period. Data collection included demographics, World Federation of Neurosurgical Surgeons score (WFNS), modified Fisher score (mFisher), admission and nadir hemoglobin (Hb) level, vasospasm, cerebral infarction, acute lung injury, and hospital mortality. The association between RBC transfusion and mortality was evaluated using a multivariate logistic regression analysis using the propensity for RBC transfusion as a covariate. RESULTS: We identified 318 patients. The median age was 54 years (46, 65), and 204 (64 %) were females. Hospital mortality was 13 % (42/318). Seventy-two (23 %) patients were transfused. Predictors of transfusion were admit and nadir Hb levels (p < 0.001), age (p = 0.02), gender (0.008), WFNS score (p < 0.001), mFisher score (p = 0.009), surgical versus endovascular treatment (p < 0.001) and moderate to severe vasospasm (p = 0.025) were predictors of transfusion. After adjustment for probability of receiving RBC transfusion, APACHE IV and nadir Hb, transfusion remained independently associated with hospital mortality (OR 3.16, 95 % CI = 1.02-9.69, p = 0.047). CONCLUSIONS: Among patients with aSAH, RBC transfusion was independently associated with an increased mortality after adjustment for the most common clinical indications for transfusion.

Impact of concomitant gastroesophageal reflux disease symptomology on prognosis and pulmonary function of chronic hypersensitivity pneumonitis.

Background and Objectives: Comorbid risk factors in chronic hypersensitivity pneumonitis (CHP) are poorly characterised. Gastroesophageal reflux disease (GERD) is linked to interstitial lung diseases like idiopathic pulmonary fibrosis (IPF), but its association and treatment in CHP is less understood. This study aims to understand the role and prevalence of GERD in CHP, plus the effect of GERD treatment on lung function and mortality. Methods: A tertiary referral centre panel was retrospectively reviewed for 214 patients diagnosed with CHP based on clinical history, bronchoalveolar lavage fluid analysis, imaging and histopathology. GERD diagnostic criteria included symptomology, acid suppressive therapy use and diagnostic testing. CHP patients with GERD (n = 89) and without GERD (n = 125) were compared via descriptive statistical analysis. Pulmonary function, GERD diagnosis plus treatment and other comorbidities were evaluated against CHP outcomes. Results: Respective differences between diagnosis and study termination dates in the GERD population versus without GERD for functional vital capacity (FVC) were - 1 L vs - 2.5 L, diffusing capacity of the lungs for carbon monoxide (DLCO) were - 2 mL/min/mmHg versus - 1 mL/min/mmHg, per cent alive at the time of study 88% versus 81%, median date of survival 574.5 versus 850 and supplemental oxygen requirement 41% versus 37%. GERD prevalence was higher in CHP patients relative to the general population. No statistical significance was found between survival curves, oxygen requirement, smoking history, FVC, or DLCO. Conclusions: GERD could be a harmful comorbidity in CHP though may not necessarily affect survival or functional outcomes. This aligns with previous IPF studies, though remains controversial. Further research is needed regarding this association and treatment benefit.

The Role of Radiology in Multidisciplinary Discussion of Patients With Interstitial Lung Diseases.

Radiologists fulfill a vital role in the multidisciplinary care provided to patients with interstitial lung diseases and other diffuse parenchymal lung disorders. The diagnosis of interstitial lung diseases hinges on the consensus of clinical, radiology, and pathology medical subspecialists, but additional expertise from rheumatology, immunology, or hematology can be invaluable. The thin-section computed tomography (CT) features of lung involvement informs the diagnostic approach. Radiologists should be familiar with radiologic methods (including inspiratory/expiratory and prone imaging) and be well versed in the recognition of the CT features of fibrosis, assessment of the overall pattern of lung involvement, and classification according to the latest guidelines. We present a case-based review that highlights examples wherein CT features and subspecialist radiologist interpretation informed the multidisciplinary team consensus diagnosis and care pathways.

A prospective, comparative trial of standard and breath-actuated nebulizer: efficacy, safety, and satisfaction.

BACKGROUND: Nebulized drug delivery is a cornerstone of therapy for obstructive lung disease, but the ideal nebulizer design is uncertain. The breath-actuated nebulizer (BAN) may be superior to conventional nebulizers. This study compared the BAN to standard nebulizer with regard to efficacy, safety, and patient and respiratory therapist (RT) satisfaction. METHODS: Adults admitted to the hospital and for whom nebulizer therapy was prescribed were enrolled. Subjects were randomly assigned to either AeroEclipse II or standard nebulizer and were surveyed at the completion of each treatment. BAN delivered albuterol 2.5 mg or albuterol 2.5 mg plus ipratropium 0.25 mg. Standard nebulizer delivered albuterol 2.5 mg or albuterol plus ipratropium 0.5 mg. An RT assessed each subject's heart rate, respiratory rate, and peak expiratory flow rate prior to and following treatment. Treatment time and adverse events were recorded. Each RT was asked to assess his/her satisfaction with each of the nebulizers. RESULTS: Twenty-eight subjects were studied. The mean age was 69 years. Fifty-four percent of the subjects indicated that overall the BAN was superior to conventional nebulizer therapy; 68% indicated that duration was preferable with the BAN. RTs were more satisfied with the BAN, based on overall performance, treatment duration, and ease of use. There were no significant differences in heart rate, peak expiratory flow rate, or respiratory rate before or after nebulization therapy with either device. The duration of treatment was significantly lower with the BAN (4.1 min vs 9.9 min, P < .001). Additionally, the BAN was associated with a lower occurrence of adverse events. CONCLUSIONS: Patients and RTs expressed greater satisfaction with the BAN, compared with standard nebulizer. Pre- and post-treatment vital signs did not differ between groups, but use of the BAN was associated with a shorter duration and a lower occurrence of adverse events. Taken together, these data support the use of the BAN for nebulized medication delivery.

Incidence and risk factors of recurrent acute lung injury.

OBJECTIVE: To determine risk factors for development of recurrent acute lung injury. DESIGN: A population-based case-control study. SETTING: The study was conducted in Olmsted County, MN, from 1999 to 2008. PATIENTS: Using a validated electronic screening protocol, investigators identified intensive care patients with acute hypoxemia and bilateral pulmonary infiltrates. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The presence of acute lung injury was independently confirmed according to American-European Consensus Conference criteria. Recurrent acute lung injury cases were subsequently matched (1:1:1) with two controls (single acute lung injury and no acute lung injury) on age, gender, duration of follow-up, and predisposing conditions. Risk factors evaluated included gastroesophageal reflux disease, alcohol consumption, smoking, chronic opioid use, and transfusions. We identified 917 patients with acute lung injury, 19 of which developed a second episode, yielding a frequency of 2.02 (95% confidence interval 1.10-2.93) per 100,000 person years. The median time to development of the second episode was 264 days (interquartile range 80-460 days), with a mortality of 47% during the episode. The history of gastroesophageal reflux disease was highly prevalent in patients who developed recurrent acute lung injury: 15 of 19 patients (79%) compared to 5 of 19 (26%) matches with a single episode of acute lung injury (p = .006) and 8 of 19 (42%) matches without acute lung injury (p = .016). Other exposures were similar between the cases and the two matched controls. CONCLUSIONS: Recurrent acute lung injury is not a rare phenomenon in the intensive care unit and may continue to increase with improvements in survival following acute lung injury. Gastroesophageal reflux disease was identified as an important risk factor for recurrent acute lung injury and may suggest an important role of gastric aspiration in the development of this syndrome.

Pulmonary vasculitis in the intensive care unit.

Pulmonary vasculitis can occur in apparent isolation, as part of a primary systemic vasculitis, or with an underlying systemic inflammatory autoimmune disorder. The presentation of pulmonary vasculitis in the intensive care unit (ICU) can be fulminant and will often overlap with more common disorders that affect the critically ill. Although diffuse alveolar hemorrhage (DAH) is the clinical feature that often initiates the concern for an underlying vasculitis, hemoptysis may not be apparent or its presentation can be mistaken for an alternative disease process. As a result, the diagnosis of pulmonary vasculitis in the ICU may be delayed or be completely unrecognized. A high level of suspicion is essential to obtain a timely diagnosis and for effective therapies to be implemented. There have been significant advances this past decade in diagnostic strategies as well as in the therapeutic options for patients with pulmonary vasculitis. We review here the clinical presentations, diagnostic strategies, and treatment options of the critically ill patients presenting with pulmonary vasculitis. The reader is referred to other resources for a more comprehensive review of specific vasculitic entities.

Particulate generation with different oxygen delivery devices.

BACKGROUND: The Coronavirus pandemic has a high mortality rate in patients that are mechanically ventilated, which has led to an ever increasing interest in noninvasive forms of oxygenation. The use of these devices has the theoretical risk of increased exposure risk because of possible particulate generation. This study aimed to quantify the particulate generation associated with different oxygen devices. METHODS: This was a prospective single center study conducted during September 2020 using ten healthy adult volunteers. Testing was conducted in a negative pressure hospital room using a light scattering particle counter. The oxygen devices used were a nasal cannula, an OxyMask™, a non-rebreathing mask, and a high flow system. Particle measurements were obtained at baseline in the room and then with each oxygen delivery device and pre-specified oxygen flow rates. These measurements were obtained different distances from the volunteer with their mouth open. A Wilcoxon/Kruskal-Wallis test was performed on each separate oxygen modality with all flow rates as one model. RESULTS: The particle concentrations were slightly non-significantly increased with the OxyMask™ and non-rebreathing mask at the closest distance measured. As the distance increased, these counts decreased closer to ambient levels. The nasal cannula and high flow nasal cannula particle counts were not significantly different from ambient measurements at either distance. CONCLUSION: Nasal cannula, OxyMask™, non-rebreathing mask, and high flow oxygen did not generate any additional aerosols or droplets above a baseline room measurement, but further studies are necessary to determine infectious risk.

Derivation and validation of a prediction model for histopathologic fibrotic hypersensitivity pneumonitis.

BACKGROUND: Clinical differentiation of fibrotic hypersensitivity pneumonitis (f-HP) remains challenging given variable and overlapping presentations with other fibrotic interstitial lung disease (f-ILD). OBJECTIVE: We derived a multivariable model for predicting histopathologic f-HP to better inform multidisciplinary team discussion (MDD) diagnosis, particularly when biopsy may be unsafe or cannot be achieved. METHODS: Patients with histopathologically-defined f-HP and other overlapping f-ILD were reviewed for distinguishing clinical and radiological variables. Using elastic net logistic regression, a penalized regression approach to minimize overfitting, a clinical model built on non-invasive assessments was derived for the prediction of histopathologic f-HP. This model was then validated in an independently derived external cohort from three sites. RESULTS: The derivation and validation cohorts consisted of 248 (84 cHP and 164 other f-ILD) and 157 (82 f-HP and 75 other f-ILD) histopathologically-defined patients, respectively (total study N = 405). Variables retained from the elastic net model included age in years (regression coefficient 0.033), male sex (-1.109), positive exposure history (1.318), percent predicted forced vital capacity (-0.021), radiologic peribronchovascular axial ILD distribution (0.199), mid (-0.22) or lower lobe (-0.839) craniocaudal or patchy (0.287) ILD distribution, upper (1.188) or equivalent upper and lower lobe (0.237) traction bronchiectasis, mosaic attenuation (1.164), and centrilobular nodules (2.045). Bias corrected AUC was 0.84 (standard error = 0.02) for the derivation cohort and 0.80 (CI 0.73-0.87) for the validation cohort. CONCLUSIONS: This multivariable model demonstrated good predictive performance for delineating histopathologically-defined f-HP from other f-ILD as a means of avoiding or justifying biopsy and supporting MDD diagnostic confidence.