Use of Quantitative CT Imaging to Identify Bronchial Thermoplasty Responders.

BACKGROUND: Bronchial thermoplasty (BT) is a treatment for patients with poorly controlled, severe asthma. However, predictors of treatment response to BT are defined poorly. RESEARCH QUESTION: Do baseline radiographic and clinical characteristics exist that predict response to BT? STUDY DESIGN AND METHODS: We conducted a longitudinal prospective cohort study of participants with severe asthma receiving BT across eight academic medical centers. Participants received three separate BT treatments and were monitored at 3-month intervals for 1 year after BT. Similar to prior studies, a positive response to BT was defined as either improvement in Asthma Control Test results of ≥ 3 or Asthma Quality of Life Questionnaire of ≥ 0.5. Regression analyses were used to evaluate the association between pretreatment clinical and quantitative CT scan measures with subsequent BT response. RESULTS: From 2006 through 2017, 88 participants received BT, with 70 participants (79.5%) identified as responders by Asthma Control Test or Asthma Quality of Life Questionnaire criteria. Responders were less likely to undergo an asthma-related ICU admission in the prior year (3% vs 25%; P = .01). On baseline quantitative CT imaging, BT responders showed less air trapping percentage (OR, 0.90; 95% CI, 0.82-0.99; P = .03), a greater Jacobian determinant (OR, 1.49; 95% CI, 1.05-2.11), greater SD of the Jacobian determinant (OR, 1.84; 95% CI, 1.04-3.26), and greater anisotropic deformation index (OR, 3.06; 95% CI, 1.06-8.86). INTERPRETATION: To our knowledge, this is the largest study to evaluate baseline quantitative CT imaging and clinical characteristics associated with BT response. Our results show that preservation of normal lung expansion, indicated by less air trapping, a greater magnitude of isotropic expansion, and greater within-lung spatial variation on quantitative CT imaging, were predictors of future BT response. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01185275; URL: www. CLINICALTRIALS: gov.

SARS-CoV-2 Rapid Antigen Testing of Symptomatic and Asymptomatic Individuals on the University of Arizona Campus.

SARS-CoV-2, the cause of COVID19, has caused a pandemic that has infected more than 80 M and killed more than 1.6 M persons worldwide. In the US as of December 2020, it has infected more than 32 M people while causing more than 570,000 deaths. As the pandemic persists, there has been a public demand to reopen schools and university campuses. To consider these demands, it is necessary to rapidly identify those individuals infected with the virus and isolate them so that disease transmission can be stopped. In the present study, we examined the sensitivity of the Quidel Rapid Antigen test for use in screening both symptomatic and asymptomatic individuals at the University of Arizona from June to August 2020. A total of 885 symptomatic and 1551 asymptomatic subjects were assessed by antigen testing and real-time PCR testing. The sensitivity of the test for both symptomatic and asymptomatic persons was between 82 and 90%, with some caveats.

Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity.

We conducted a serological study to define correlates of immunity against SARS-CoV-2. Compared to those with mild coronavirus disease 2019 (COVID-19) cases, individuals with severe disease exhibited elevated virus-neutralizing titers and antibodies against the nucleocapsid (N) and the receptor binding domain (RBD) of the spike protein. Age and sex played lesser roles. All cases, including asymptomatic individuals, seroconverted by 2 weeks after PCR confirmation. Spike RBD and S2 and neutralizing antibodies remained detectable through 5-7 months after onset, whereas α-N titers diminished. Testing 5,882 members of the local community revealed only 1 sample with seroreactivity to both RBD and S2 that lacked neutralizing antibodies. This fidelity could not be achieved with either RBD or S2 alone. Thus, inclusion of multiple independent assays improved the accuracy of antibody tests in low-seroprevalence communities and revealed differences in antibody kinetics depending on the antigen. We conclude that neutralizing antibodies are stably produced for at least 5-7 months after SARS-CoV-2 infection.

Detection, prevalence, and duration of humoral responses to SARS-CoV-2 under conditions of limited population exposure.

We conducted an extensive serological study to quantify population-level exposure and define correlates of immunity against SARS-CoV-2. We found that relative to mild COVID-19 cases, individuals with severe disease exhibited elevated authentic virus-neutralizing titers and antibody levels against nucleocapsid (N) and the receptor binding domain (RBD) and the S2 region of spike protein. Unlike disease severity, age and sex played lesser roles in serological responses. All cases, including asymptomatic individuals, seroconverted by 2 weeks post-PCR confirmation. RBD- and S2-specific and neutralizing antibody titers remained elevated and stable for at least 2-3 months post-onset, whereas those against N were more variable with rapid declines in many samples. Testing of 5882 self-recruited members of the local community demonstrated that 1.24% of individuals showed antibody reactivity to RBD. However, 18% (13/73) of these putative seropositive samples failed to neutralize authentic SARS-CoV-2 virus. Each of the neutralizing, but only 1 of the non-neutralizing samples, also displayed potent reactivity to S2. Thus, inclusion of multiple independent assays markedly improved the accuracy of antibody tests in low seroprevalence communities and revealed differences in antibody kinetics depending on the viral antigen. In contrast to other reports, we conclude that immunity is durable for at least several months after SARS-CoV-2 infection.

COPD: To Be or Not to Be, That is the Question.

As our knowledge on the natural history of chronic obstructive pulmonary disease (COPD) progresses, a conceptual model simply based on an accelerated decline of lung function in adult life in response to smoking has become inadequate to capture the complexity of this disease, and increasing attention is being given to possible contributions from events or alterations of developmental processes that take place earlier in life. In addition, a remarkable heterogeneity has emerged among the pathobiological mechanisms that are involved in different phenotypes of COPD, suggesting that an effective disease management will require individualized treatment approaches largely based on the underlying biological mechanisms (endotypes). In this review, we will discuss the many faces of COPD from an epidemiological, pathobiological, and clinical standpoint and argue that airflow limitation encompasses a number of manifestations that are too diverse to be still clustered under the same diagnostic label.

Endobronchial Valves Therapy for Advanced Emphysema: A Meta-Analysis of Randomized Trials.

BACKGROUND: Trials suggest that bronchoscopic lung volume reduction (BLVR) with endobronchial valve (EBV) implantation may produce similar effects as lung volume reduction surgery, by inducing atelectasis and reducing hyperinflation through a minimally invasive procedure. This study sought to investigate the efficacy and safety of BLVR with EBV for advanced emphysema. METHODS: We searched PubMed, EMBASE, Web of Science, CINAHL, ClinicalTrials.gov, and Cochrane Library databases for randomized controlled trials comparing EBV implantation versus standard medical treatment or sham bronchoscopy. The main outcome of interest was the percentage change of forced expiratory volume in 1 second. RESULTS: Data analyzed from 5 randomized controlled trials with 703 patients revealed improvement in percentage change of forced expiratory volume in 1 second in EBV group compared with control group [weighted mean difference (WMD)=11.43; 95% confidence interval (CI), 6.05-16.80; P<0.0001] and improvement in the St. George's Respiratory Questionnaire score (WMD=-5.69; 95% CI, -8.67 to -2.70; P=0.0002). There is no difference shown in the 6-minute walking test (WMD=14.12; 95% CI, -4.71 to 32.95; P=0.14). The overall complication rate of EBV was not significantly different except for an increased rate of pneumothorax [relative risk (RR)=8.16; 95% CI, 2.21-30.11; P=0.002), any hemoptysis (RR=5.01; 95% CI, 1.12-22.49; P=0.04)] and valve migration (RR=8.64; 95% CI, 2.01-37.13; P=0.004). CONCLUSION: BLVR using EBV shows short-term improvement in lung function and quality of life, but with increased risk of minor hemoptysis, pneumothorax, and valve migration. Follow-up data on the studies are needed to determine its long-term efficacy.

Refill rates of accessories for positive airway pressure therapy as a surrogate measure of long-term adherence.

STUDY OBJECTIVES: To identify and validate a surrogate measure of long-term adherence to positive airway pressure (PAP) therapy in patients with obstructive sleep apnea (OSA). DESIGN: Retrospective cohort study. SETTING: Academic center. PARTICIPANTS: 220 consecutive patients with OSA. INTERVENTIONS: N/A. MEASUREMENTS: In patients with OSA who were receiving PAP therapy (for > 1 year), PAP adherence measured by device-download and defined by Medicare criteria was compared to refill rates for mask and other PAP therapy accessories. First, receiver operating characteristic (ROC) curves were constructed to identify a threshold value of refills per year that discriminated best between PAP adherent and non-adherent patients (derivation set; n = 100). Then the predictive accuracy of the threshold value of refills per year was tested in an additional 120 consecutive patients (validation set). RESULTS: From the derivation set, ROC curve with good discriminant characteristics (ROC 0.83; 95% confidence intervals [CI], 0.75, 0.91, p < 0.0001) was used to identify a threshold value of refills (0.7 refills/year) for distinguishing PAP adherent and non-adherent patients. Subsequently, when the threshold was applied to the validation set, the likelihood ratio for a positive test (weighted for prevalence) predicting adherence to PAP therapy was 7.3 (95%CI, 3.8, 14), and likelihood ratio for a negative test was 0.6 (95%CI; 0.4, 0.8). CONCLUSION: Refill rate of PAP accessories exhibited good test characteristics for predicting long-term PAP adherence. Such a surrogate measure based upon insurance claims data can be a powerful epidemiological tool in bioinformatics-aided comparative-effectiveness research and to monitor clinical performance of health systems.