New research was presented at ATS 2019, The annual American Thoracic Society International Conference, from May 17-22 in Dallas. The features below highlight some of the studies presented at the conference, focusing on those of interest to pulmonologists and allergists & immunologists.
Improved Airway Wall Measurement Accuracy
Although airway disease is one of the pathologic processes defining COPD, measures of wall thickness on CT to assess this process are generally inaccurate due to the lack of resolution, this limiting the use of wall thickening as an airway phenotype in COPD investigations. Researchers conducted a study to asses a novel approach to measuring airway wall thickness on chest CT that they hoped would improve the assessment of expiratory airflow obstruction. For the novel approach, a 2D convolutional neural network (CNN) was trained on 2.5 million synthetic airway patches of 32×32 pixels, resembling real airways of different sizes to regress the airway lumen and wall thickness values in millimeters. Airway synthesis was performed using a geometric model. For validation, the study team computed the relative error (RE) between the automatic measurement of 200,000 synthetic patches and the ground truth of the geometric model. They then used COPDGene data to compare the correlation between Pi10, a measurement of wall thickeneing, and FEV1 obtained using their technique (CNN-Pi10) and a standard method (Std-Pi10). The mean RE of the synthetic patches was 4.90%. Pearson’s correlation coefficients between Pi10 and FEV1 were -0.51 for CNN and -0.33 for the standard method. The correlation between Pi10 and functional small airway disease was 0.401 for CNN-Pi10 and 0.0862 for Std-Pi10. The study authors concluded that the CNN “method is robust and improves results obtained with standard methods, better explaining lung function decline in smokers.”
Tech to Optimize Pediatric PAP Adherence
Although engagement tools supported by web-based programs and smartphone apps have been developed to address adherence to positive airway pressure (PAP) in adults with obstructive sleep apnea (OSA), data are lacking on their effectiveness in children and adolescents. For a study, researchers analyzed data from a cloud-based technology that stores data derived from PAP devices on a nightly basis to help clinicians remotely monitor PAP adherence. Patients with OSA in the study were aged 4 to 18 and participants in a patient engagement program (PEP) that uses a score incorporating usage hours, mask seal indicating leak level, respiratory events per hour of usage, and number of times the PAP mask is taken on/off. Based on these scores, patients were provided with feedback aimed at optimizing adherence, with personalized coaching designed to improve self-management sent via email or through a smartphone app. Among more than 20,000 children, PEP was activated in 20.0%, among whom 90-day adherence with PAP was 63.2%, compared with 42.1% for non-PEP users. PEP was associated with significantly improved patient adherence at 90 days.
Post-COPD Hospitalization Pulmonary Rehab & 1-Year Mortality
Although meta-analyses indicate that pulmonary rehabilitation (PR) following a COPD exacerbation can help improve quality of life and reduce both readmission and mortality risk, the total number of patients studied is relatively small, with high rates of heterogeneity across the analyzed trials. To determine the association between initiation, dose, and timing of PR following hospital discharge and 1-year survival, conducted a retrospective cohort study of all fee-for-service Medicare beneficiaries aged 66 or older who were hospitalized for COPD exacerbation in 2012. Patients who initiated PR within 90 days of discharge were matched with those who did not. Patients who completed 18 or more PR sessions were compared with those who completed fewer, while early initiators (<42 days) were compared with late initiators (43-90 days). Among more than 124,000 patients, only 2.7% initiated PR within 90 days. Those who did were younger, had fewer comorbidities, and were less likely to visit an ER or be hospitalized between discharge and PR initiation, but more likely to receive home oxygen. PR was associated with a lower risk of 1-year mortality in the matched cohort, and those who completed 18 or more sessions had a lower mortality risk than those who completed fewer. However, initiation within 6 weeks of discharge was associated with a higher mortality risk.
Mortality Patterns Among Coal Miners
Although the US Department of Labor collects data on coal miners applying for Federal Black Lung Program benefits, mortality data from this population has yet to be analyzed. For a study, researchers examined non-malignant respiratory diseases (NMRD), pneumoconiosis excluding asbestosis, COPD, lung cancer, and ischemic heart disease as cause of death among US coal miners from the National Death Index on former US coal miners who previously applied for federal benefits between 1970 and 2016 and had participated in the National Coal Workers’ Health Surveillance Program. NMRD accounted for 20% of the underlying cause of death in the study population, with proportional mortality from NMRD increasing significantly among those aged 65-74 born after 1930 (1930-1939, 28%; 1940-1970, 32%) when compared with those born before 1930. A similar trend was seen with COPD-related deaths also. Proportional mortality from NMRD, especially pneumoconiosis, among those younger than 65 increased significantly in the most recent birth cohort when compared with earlier birth cohorts. Proportional mortality from lung cancer was significantly elevated among older participants (19%) in the most recent birth cohort (1940 and after) when compared with those of the same age in previous cohorts (7-11%).
A Better Predictor of Childhood Asthma
With a lack of better alternatives, clinicians must rely on poorly predictive asthma outcome tools, resulting in asthma phenotypes not being amenable to primary prevention or early intervention. Using data from the Cincinnati Childhood Allergy and Air Pollution Study, study investigators identified factors that predicted asthma development with the hopes of developing a quantitative personalized tool to predict asthma development in young children. By integrating demographic and clinical data, they constructed the Pediatric Asthma Risk Score (PARS), and compared its sensitivity and specificity with those of the Asthma Predictive Index (API) and replicated in the Isle of Wight birth cohort. In predicting asthma development in the data source study, PARS had a sensitivity of 0.68 and a specificity of 0.77. While both PARS and API predicted asthma in high-risk children, PARS had improved ability to do so in those with mild-to-moderate risk. Along with parental asthma, eczema, and wheezing apart from colds, early wheezing, sensitization to two or more food allergens and/or aeroallergens, and African-American race predicted asthma in PARS. PARS was replicated in the Isle of Wight birth cohort with a sensitivity of 0.67 and a specificity of 0.79.
Mold Antigen Extracts Miss the Mark
Evidence suggests that species-specific mold antigen extracts used to assess clinically suspected mold-related conditions may not be aligned with the species of mold identified in the indoor and outdoor environment. Researchers conducted a study to identify the predominant genera and species of molds in the air of homes with water damage, mold growth, and/or occupants with respiratory complaints from regions throughout the US and Canada and to assess the concordance between these genera and species and the mold antigen extracts used at major clinical laboratories and antigen extract manufacturers for serum and skin testing. The predominant genera and species of molds identified in complaint homes were poorly aligned with the species-specific mold antigen extracts currently used by clinicians to assess mold allergies. For the Aspergillus and Penicillium genera, more than 50% and more than 80% of the fungal organisms found in complaint homes, respectively, were species that were absent from the antigen extracts used by clinicians.
Novel Biomarkers of Allergic Bronchopulmonary Aspergillosis
Data indicate that he incidence of allergic bronchopulmonary aspergillosis (ABPA) is increasing in the US. With delayed recognition possibly resulting in significant morbidity and mortality, prompt and early diagnosis is needed. With thymocyte and activation-regulated chemokine (TARC) and thymic stromal lymphopoietin (TSLP) having been postulated in various allergic disorders, researchers sought to determine and compare the serum TARC and TSLP levels of patients with ABPA aged 5-15 with those of controls. Among all participants, pulmonary function test (PFT), total IgE levels, Aspergillus-specific IgE leves, serum TARC, and TSLP levels were assessed. At baseline, 65% of ABPA group had total IgE levels above 5,000 kU/L and a mean Aspergillus-specific IgE level of 32.09 kUA/L. Mean TARC levels were 980.515 pg/ml in the ABPA group and 500.69 pg/ml in the non-ABPA group, a statistically significant difference. Mean TSLP levels were 904.947 pg/ml in the ABPA group and 696.669 pg/ml in the non-ABPA group, a difference that is not statistically significant. Area under the curve for serum TARC was 0.827, implying a good diagnostic accuracy and leading the study authors to conclude that serum TARC may have a potential role as a biomarker for the diagnosis of ABPA, whereas serum TSLP appears to have a limited role.
Real-World Management of ABPM
Evidence suggests that most cases of allergic bronchopulmonary mycosis (ABPM) are treated with corticosteroids, antifungals, or both. However, the most effective treatment for ABPM remains unknown. To examine real-world practices in ABPM treatment, the clinical findings and treatment of ABPM cases that had been diagnosed and treated at a single hospital between 2010 and 2018 were investigated for a small study. Among 31 cases, eosinophil levels in peripheral blood were 0.3% to 51.2%, with a median of 14%. Fungi were detected in approximately one-half of cases. Among 23 patients administered corticosteroids, five received these drugs only and 18 received them in combination with itraconazole. Four patients were treated with itraconazole only. Although all cases improved with treatment, 10 relapses occurred in the steroid group, compared with just one in the non-steroid group. Median eosinophil levels were 15.9% in the steroid group and 11.7% in the non-steroid group.
Identifying Upper Airway Disease Susceptibility
Prior research suggests that genetic variability in sinus immune functions may contribute to sinusitis disease vulnerability or disease severity. The minor variant of pulmonary surfactant protein A2 (SP-A2) is expressed heterozygously in more than 30% of people (SP-A2 Gln223 allele A/C), with about 5% homozygous for Gln at position 223 of SP-A2 (allele C/C). The single nucleotide polymorphism (SNP) rs1965708 has been shown in other studies to be associated with increased risk for tuberculosis, high altitude pulmonary edema, and allergic rhinitis. To test the hypothesis that SP-A2 SNP rs1965708 plays a role in sinusitis prevalence, study investigators extracted genomic DNA from buccal swabs or saliva samples from patients with chronic rhinosinusitis (CRS) and matched healthy subjects. The minor variant of the SNP was expressed heterozygously (SP-A2 Gln223 allele A/C) in 44.59% and homozygously in 5.41% of the cohort. The SNP significantly increased the odds for CRS and for polyposis. The study authors concluded that “SP-A2 aa223 rs1965708 SNP is significantly associated with prevalence of upper airway disease” and that since it “corresponds to the SP-A2 carbohydrate domain that binds bacterial surface phosphatidylglycerosis and affects its bacteriostatic effect, it is likely that individuals with the recessive allele are more prone to bacterial sinus infections.”