Cluster Analysis of World Trade Center Related Lower Airway Diseases.

ABSTRACT: Introduction: Cluster analysis can classify without a priori assumptions the heterogeneous chronic lower airway diseases found in former workers at the World Trade Center (WTC) disaster site. Methods: We selected the first available chest computed tomography scan with quantitative computed tomography measurements on 311 former WTC workers with complete clinical, and spirometric data from their closest surveillance visit. We performed a nonhierarchical iterative algorithm K-prototype cluster analysis, using gap measure. Results: A five-cluster solution was most satisfactory. Cluster 5 had the healthiest individuals. In cluster 4, smoking was most prevalent and intense but there was scant evidence of respiratory disease. Cluster 3 had symptomatic subjects with reduced forced vital capacity impairment (low FVC). Clusters 1 and 2 had less dyspneic subjects, but more functional and quantitative computed tomography evidence of chronic obstructive pulmonary disease (COPD) in cluster 1, or low FVC in cluster 2. Clusters 1 and 4 had the highest proportion of rapid first-second forced expiratory volume decliners. Conclusions: Cluster analysis confirms low FVC and COPD/pre-COPD as distinctive chronic lower airway disease phenotypes on long-term surveillance of the WTC workers.

Postoperative CT surveillance in the evaluation of local recurrence after sub-lobar resection of neoplastic lesions of the lung.

OBJECTIVE: As indications for sub-lobar resections increase, it will become more important to identify risk factors for postsurgical recurrence. We investigated retrospectively the association between local recurrence after sub-lobar resection of neoplastic lung lesions and pre- and post-operative CT imaging and pathologic features. MATERIALS AND METHODS: We reviewed retrospectively neoplastic lung lesions with postoperative chest CT surveillance of sub-lobar resections in 2006-2016. We defined "suspicious" findings as nodularity ≥3 mm or soft tissue thickening ≥4 mm along the suture line and/or progression and explored their association with local recurrence. Primary lung cancer stage, tumoral invasion of lymphatics, visceral pleura or large vessels, bronchial and vascular margin distance were also assessed. RESULTS: Our study group included 45 cases of sub-lobar resection took for either primary (n = 37) or metastatic (n = 8) lung tumors. Local recurrence was observed in 16 of those patients. New nodularity ≥3 mm or soft tissue thickening ≥4 mm along the suture line on surveillance CT was significantly associated with local recurrence (p = 0.037). Additionally, solid nodule (p = 0.005), age at surgery ≤60 years (p = 0.006), two or more sites of invasion (p < 0.0001) and poor histologic differentiation (p = 0.0001) were also significantly associated with local tumor recurrence. Of 16 patients with surveillance post-surgical PET-CT, 15 had elevated FDG uptake. CONCLUSION: The postoperative changes along the suture line should follow a predictable time course demonstrating a pattern of stability, thinning or resolution on CT surveillance. New or increasing postoperative nodularity ≥3 mm or soft tissue thickening ≥4 mm along the suture line requires close diagnostic work-up. Surgical pathology characteristics added prognostic value on postoperative recurrence surveillance.

Association of World Trade Center (WTC) Occupational Exposure Intensity with Chronic Obstructive Pulmonary Disease (COPD) and Asthma COPD Overlap (ACO).

INTRODUCTION: Reported associations between World Trade Center (WTC) occupational exposure and chronic obstructive pulmonary disease (COPD) or asthma COPD overlap (ACO) have been inconsistent. Using spirometric case definitions, we examined that association in the largest WTC occupational surveillance cohort. METHODS: We examined the relation between early arrival at the 2001 WTC disaster site (when dust and fumes exposures were most intense) and COPD and ACO in workers with at least one good quality spirometry with bronchodilator response testing between 2002 and 2019, and no physician-diagnosed COPD before 9/11/2001. COPD was defined spirometrically as fixed airflow obstruction and ACO as airflow obstruction plus an increase of ≥ 400 ml in FEV1 after bronchodilator administration. We used a nested 1:4 case-control design matching on age, sex and height using incidence density sampling. RESULTS: Of the 17,928 study participants, most were male (85.3%) and overweight or obese (84.9%). Further, 504 (2.8%) and 244 (1.4%) study participants met the COPD and ACO spirometric case definitions, respectively. In multivariable analyses adjusted for smoking, occupation, cohort entry period, high peripheral blood eosinophil count and other covariates, early arrival at the WTC site was associated with both COPD (adjusted odds ratio [ORadj] = 1.34, 95% confidence interval [CI] 1.01-1.78) and ACO (ORadj = 1.55, 95%CI 1.04-2.32). CONCLUSION: In this cohort of WTC workers, WTC exposure intensity was associated with spirometrically defined COPD and ACO. Our findings suggest that early arrival to the WTC site is a risk factor for the development of COPD or of fixed airway obstruction in workers with pre-existing asthma.

Occupational lung disease: when should I think of it and why is it important?

Exposure to toxic inhalants in the workplace has the potential to cause (in susceptible individuals) almost any major type of lung disease, such as asthma, COPD and interstitial lung diseases. Patients with occupational lung disease will often present to or will be managed by respiratory specialists without training in occupational respiratory medicine, and patients (or their clinicians) may not identify a link between their disease and their current or a past job. Without an awareness of the range of different occupational lung diseases that exist, their similarity to their non-occupational counterparts, and without directed questioning, these conditions may go unidentified. Patients with occupational lung diseases are often in lower paid work and are disproportionally affected by health inequality. Both clinical and socioeconomic outcomes generally improve if cases are identified early. This allows appropriate advice to be given about the risks of ongoing exposure, clinical management, occupational mobility and, in some cases, eligibility for legal compensation. As respiratory professionals, it is important that these cases are not missed, and if needed, are discussed with a physician with specialised expertise. Here we describe some of the most common occupational lung diseases and outline the diagnostic and treatment approach.

Transmission and Risk Factors of COVID-19 among Health Care Workers.

Coronavirus disease 2019 (COVID-19) poses a significant occupational risk factor to health care workers (HCWs). As in previous events, this occupational risk amplifies and compounds the adverse impact of the pandemic. We conducted a narrative review summarizing risk factors associated with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) transmission in HCWs. We searched for original observational studies (including case-control, cross-sectional, prospective and retrospective cohorts) using PubMed, Scopus, and Google Scholar. A total of 22 articles were reviewed, including eligible English articles published between April 2020 and May 2022. Job category, work environment, personal protective equipment (PPE) noncompliance, lack of PPE awareness and training, unvaccinated status, and competing community and household exposures were identified as risk factors for SARS-CoV-2 transmission among HCWs. Effective measures to protect HCWs from SARS-CoV-2 need to account for the identified occupational risk factors. Identifying and understanding COVID-19 risk factors among HCWs must be considered a public health priority for policy makers to mitigate occupational and community transmission in current and future epidemics.

World Trade Center Health Program best practices for the diagnosis and treatment of fibrosing interstitial lung diseases.

Interstitial lung diseases (ILDs) are a diverse set of related conditions with multiple etiologies, in addition to a group where the cause is unknown. There is concern for a potential association of WTC-related exposures with ILD, but the disease range has not differed from what is observed in the general population, and active investigations to study that association are ongoing. Although these diseases are very diverse, some are extremely rare, and they often are disabling and have a poor prognosis, evidence-based guidelines for their diagnosis, management and long-term monitoring have emerged and will evolve as knowledge and therapeutic options increase. This brief article summarizes pertinent issues of diagnosis and management of ILDs, applicable to the diverse group of ILDs that have been observed in the WTC Health Program covered population.

World Trade Center Health Program best practices for diagnosing and treating chronic rhinosinusitis.

The most frequent adverse physical health effect among World Trade Center Health Program (WTCHP) members is chronic rhinosinusitis (CRS), with some evidence supporting its association with the exposures to dust, gases, and toxicants. We selected the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICARS-RS-2021) as a comprehensive evidence-based guide on best practices for CRS diagnosis and treatment for the WTCHP.

World Trade Center Health Program best practices for diagnosing and treating chronic obstructive pulmonary disease.

World Trade Center exposures may have the potential to cause or aggravate chronic obstructive pulmonary disease (COPD). The WTC Health Program covers the entire range of clinical services for COPD, following the 2021 diagnostic and treatment guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD).

Change in Asthma Is Associated with Change in PTSD in World Trade Center Health Registrants, 2011 to 2016.

The WTC Health Registry (WTCHR) is a closed, longitudinal cohort of rescue/recovery workers and survivors exposed to the 11 September 2001 disaster. WTCHR enrollees diagnosed with asthma after 11 September 2001 continued to experience poor control despite treatment. Asthma is associated with mental problems, although their bidirectional movement has not been studied. This study tested whether a clinical change in mental problems was associated with a difference in asthma control, and whether a change in asthma control varied with a change in quality of life (QoL). Difference in the Asthma Control Test (ACT) on the WTCHR from 2011-12 to 2015-16 was compared with the change in the Post-traumatic Stress Disorder Checklist (PCL-17), the Patient Health Questionnaire depression scale, self-reported heartburn, and change of physical and mental QoL over this period. In adjusted multinomial multivariable logistic regression, improved PCL-17 was associated with a better ACT score, odds ratio (OR) = 1.42 (95% C.I. 1.01, 1.99), and a worsened PCL-17 score was associated with a worsened ACT score, OR = 1.77 (95% C.I. 1.26, 2.50). Decreased ACT was associated with poor physical QoL, OR = 1.97 (95% C.I. 1.48, 2.62). Change in mental health measures tracked with change in asthma control, which correlated with a change in QoL. Careful follow-up and treatment of all three are indicated to improve these inter-related issues.

Lung cancer incidence among world trade center rescue and recovery workers.

BACKGROUND: Many World Trade Center disaster (WTC) rescue and recovery workers (WTC RRWV) were exposed to toxic inhalable particles. The impact of WTC exposures on lung cancer risk is unclear. METHODS: Data from the WTC Health Program General Responders Cohort (WTCGRC) were linked to health information from a large New York City health system to identify incident lung cancer cases. Incidence rates for lung cancer were then calculated. As a comparison group, we created a microsimulation model that generated expected lung cancer incidence rates for a WTC- and occupationally-unexposed cohort with similar characteristics. We also fitted a Poisson regression model to determine specific lung cancer risk factors for WTC RRWV. RESULTS: The incidence of lung cancer for WTC RRWV was 39.5 (95% confidence interval [CI]: 30.7-49.9) per 100,000 person-years. When compared to the simulated unexposed cohort, no significant elevation in incidence was found among WTC RRWV (incidence rate ratio [IRR] 1.34; 95% CI: 0.92-1.96). Predictors of lung cancer incidence included age, smoking intensity, and years since quitting for former smokers. In adjusted models evaluating airway obstruction and individual pre-WTC occupational exposures, only mineral dust work was associated with lung cancer risk (IRR: 2.03; 95% CI: 1.07-3.86). DISCUSSION: In a sample from a large, prospective cohort of WTC RRWV we found a lung cancer incidence rate that was similar to that expected of a WTC- and occupationally-unexposed cohort with similar individual risk profiles. Guideline-concordant lung cancer surveillance and periodic evaluations of population-level lung cancer risk should continue in this group.

Violence-related distress and lung function in two longitudinal studies of youth.

BACKGROUND: Exposure to violence has been associated with lower lung function in cross-sectional studies. METHODS: We examined whether increasing violence-related distress over time is associated with worse lung function and worse asthma control or quality of life in a secondary analysis of a 48-week randomised clinical trial in 98 youth with asthma (aged 9-16 years) treated with low-dose inhaled corticosteroids (Vitamin D Kids Asthma Study (VDKA)). We then replicated our findings for lung function in a prospective study of 232 Puerto Rican youth followed for an average of 5.4 years. Violence-related distress was assessed using the Checklist of Children's Distress Symptoms (CCDS) scale. Our outcomes of interest were percent predicted lung function measures and (in VDKA only) asthma control (assessed using the Asthma Control Test) and asthma-related quality of life (assessed using the Pediatric Asthma Quality of Life Questionnaire (PAQLQ)). RESULTS: In a multivariable analysis in VDKA, each 1-point increment in CCDS score was associated with decrements of 3.27% in forced expiratory volume in 1 s (FEV1) % pred (95% CI -6.44- -0.22%; p=0.04), 2.65% in forced vital capacity (FVC) % pred (95% CI -4.86- -0.45%; p=0.02) and 0.30 points in the overall PAQLQ score (95% CI -0.50- -0.10 points; p<0.01). Similar findings for FEV1 and FVC were obtained in the prospective study of Puerto Rican youth. CONCLUSIONS: Our findings suggest that violence-related distress may worsen lung function and quality of life in youth with asthma (even those treated with low-dose inhaled corticosteroids), and further support policies to reduce exposure to violence among children in the USA and Puerto Rico.

Time to a Negative SARS-CoV-2 PCR Predicts Delayed Return to Work After Medical Leave in COVID-19 Infected Health Care Workers.

OBJECTIVE: To investigate whether HCWs return to work (RTW) after COVID-19 was associated with time to a negative viral detection test. METHODS: To evaluate the association of RTW with an undetectable RT-PCR adjusting for different factors. RESULTS: Three hundred seventy-five HCWs who required medical leave for COVID-19 at a hospital in Madrid. Multivariable analyses confirmed the association of delayed RTW with interval to negative PCR (ORadj 1.12, 95% CI 1.08, 1.17) as well as age, sex, and nursing staff and clinical support services compared to physicians. A predictive model based on those variables is proposed, which had an area under the receiver operating curve of 0.82. CONCLUSIONS: Delayed RTW was associated with longer interval to a negative RT-PCR after symptom onset, adjusting for occupational category, age, and sex.

COVID-19 as an occupational disease.

The impact of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 permeates all aspects of society worldwide. Initial medical reports and media coverage have increased awareness of the risk imposed on healthcare workers in particular, during this pandemic. However, the health implications of COVID-19 for the global workforce are multifaceted and complex, warranting careful reflection and consideration to mitigate the adverse effects on workers worldwide. Accordingly, our review offers a framework for considering this topic, highlighting key issues, with the aim to prompt and inform action, including research, to minimize the occupational hazards imposed by this ongoing challenge. We address respiratory disease as a primary concern, while recognizing the multisystem spectrum of COVID-19-related disease and how clinical aspects are interwoven with broader socioeconomic forces.

Asthma-COPD overlap in World Trade Center Health Registry enrollees, 2015-2016.

INTRODUCTION: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a newly redefined form of chronic airway disease and has not been well studied among 9/11-exposed populations with increased prevalence of asthma. We assessed the prevalence and risk factors associated with ACO in an exposure cohort of World Trade Center Health Registry (WTCHR) enrollees. METHODS: This is a longitudinal study, including enrollees with complete data on 9/11/01 exposure at enrollment (2003-2004, Wave 1), asthma and COPD diagnoses and at least 25 years of age at the time of the 2015-2016 (Wave 4) WTCHR survey. Probable ACO was defined as self-reported post-9/11 physician-diagnosed asthma and either emphysema, chronic bronchitis, or COPD. We evaluated whether probable ACO was associated with World Trade Center (WTC)-related exposures, using multivariable logistic regression. RESULTS: Of 36,864 Wave 4 participants, 29,911 were eligible for this analysis, and 1,495 (5.0%) had self-reported post-9/11 probable ACO. After adjusting for demographics and smoking status, we found 38% increased odds of having ACO in enrollees with exposure to the dust cloud, and up to 3.39 times the odds in those with ≥3 injuries sustained on 9/11. Among rescue/recovery workers, ever working on the pile, on the pile on 9/11 or 9/12/01, or working on the WTC site for >7 days showed increased odds ratios of having ACO. CONCLUSION: Probable ACO is associated with WTC exposures. Further study of ACO is needed to understand the development of this and other environmentally or occupationally-related airway diseases, and how to prevent these in disasters like 9/11.

Association of quantitative CT lung density measurements and lung function decline in World Trade Center workers.

BACKGROUND: Occupational exposures at the WTC site after 11 September 2001 have been associated with presumably inflammatory chronic lower airway diseases. AIMS: In this study, we describe the trajectories of expiratory air flow decline, identify subgroups with adverse progression, and investigate the association of those trajectories with quantitative computed tomography (QCT) imaging measurement of increased and decreased lung density. METHODS: We examined the trajectories of expiratory air flow decline in a group of 1,321 former WTC workers and volunteers with at least three periodic spirometries, and using QCT-measured low (LAV%, -950 HU) and high (HAV%, from -600 to -250 HU) attenuation volume percent. We calculated the individual regression line slopes for first-second forced expiratory volume (FEV1 slope), identified subjects with rapidly declining ("accelerated decliners") and increasing ("improved"), and compared them to subjects with "intermediate" (0 to -66.5 mL/year) FEV1 slope. We then used multinomial logistic regression to model those three trajectories, and the two lung attenuation metrics. RESULTS: The mean longitudinal FEV1 slopes for the entire study population, and its intermediate, decliner, and improved subgroups were, respectively, -40.4, -34.3, -106.5, and 37.6 mL/year. In unadjusted and adjusted analyses, LAV% and HAV% were both associated with "accelerated decliner" status (ORadj , 95% CI 2.37, 1.41-3.97, and 1.77, 1.08-2.89, respectively), compared to the intermediate decline. CONCLUSIONS: Longitudinal FEV1 decline in this cohort, known to be associated with QCT proximal airway inflammation metric, is also associated with QCT indicators of increased and decreased lung density. The improved FEV1 trajectory did not seem to be associated with lung density metrics.

PAP Adherence and Nasal Resistance. A Randomized Controlled Trial of CPAPflex versus CPAP in World Trade Center Responders.

Rationale: Continuous positive airway pressure (CPAP) adherence is often poor in obstructive sleep apnea (OSA) and may be influenced by nasal resistance. CPAP with a reduction of expiratory pressure (CPAPflex) may reduce discomfort in those with high nasal resistance and improve adherence in this subgroup.Objectives: To evaluate the association of positive airway pressure (PAP) treatment adherence to nasal resistance and examine if CPAPflex improves adherence over CPAP in subjects with high nasal resistance.Methods: A randomized double-blind crossover trial of 4 weeks each of CPAPflex versus CPAP in subjects exposed to World Trade Center dust with OSA stratified by nasal resistance, measured by 4-Phase Rhinomanometry.Results: Three hundred seventeen subjects with OSA (mean, apnea-hypopnea index with 4% O2 desaturation for hypopnea = 17 ± 14/h) were randomized. Overall, PAP adherence was poor, but adherence to CPAP (n = 239; mean hours per night [95% confidence interval (CI)]), 1.97 h (1.68 to 2.26) was greater than adherence to CPAPflex (n = 249; 1.65 h [1.39 to 1.91]; difference of 0.31 h [0.03; 0.6]; P < 0.05). Contrary to our hypothesis there was no correlation between nasal resistance and adherence to CPAP (r = 0.098; P = not significant) or CPAPflex (r = 0.056; P = not significant). There was no difference in adherence between CPAP and CPAPflex (mean Δ hours [95% CI]) in subjects with low resistance (0.33 h [-0.10 to 0.76]) or high nasal resistance (0.26 h [-0.14 to 0.66]). No significant differences were observed in any of the secondary outcomes between PAP modes.Conclusions: Contrary to expectations, our data do not show better adherence to CPAPflex than to CPAP in subjects with high or low nasal resistance and do show clinically insignificant better adherence overall with CPAP.Clinical trial registered with www.clinicaltrials.gov (NCT01753999).

Association of low FVC spirometric pattern with WTC occupational exposures.

BACKGROUND: A reduced forced vital capacity without obstruction (low FVC) is the predominant spirometric abnormality reported in workers and volunteers exposed to dust, gases, and fumes at the World Trade Center (WTC) disaster site in 2001-2002. While low FVC has been associated with obesity and metabolic syndrome, its association with WTC occupational exposures has not been demonstrated. We estimated the prevalence of this abnormality and examined its association with WTC exposure level. METHODS: Longitudinal study of the relation between arrival at the WTC site within 48 h and FVC below the lower limit of normal (FVC < LLN, with normal FEV1/FVC ratio) at any time in 10,284 workers with at least two spirometries between 2002 and 2018. Logistic regression and linear mixed models were used for the multivariable analyses. RESULTS: The prevalence of low FVC increased from 17.0% (95% CI 15.4%, 18.5%) in June 2003, to 26.4% (95% CI 24.8%, 28.1%) in June 2018, and exceeded at both times that of obstruction. The rate of FVC decline was -43.7 ml/year during the study period. In a multivariable analysis adjusting for obesity, metabolic syndrome indicators, and other factors, early arrival at the WTC disaster site was significantly associated with low FVC, but only among men (ORadj = 1.29, 95% CI 1.17, 1.43). Longitudinal FVC rate of decline did not differ by WTC site arrival time. CONCLUSIONS: Among WTC workers, the prevalence of low FVC increased over a 16-year period. Early arrival to the WTC disaster site was significantly associated with low FVC in males.

Quantitative CT Evidence of Airway Inflammation in WTC Workers and Volunteers with Low FVC Spirometric Pattern.

BACKGROUND: The most common abnormal spirometric pattern reported in WTC worker and volunteer cohorts has consistently been that of a nonobstructive reduced forced vital capacity (low FVC). Low FVC is associated with obesity, which is highly prevalent in these cohorts. We used quantitative CT (QCT) to investigate proximal and distal airway inflammation and emphysema in participants with stable low FVC pattern. METHODS: We selected study participants with at least two available longitudinal surveillance spirometries, and a chest CT with QCT measurements of proximal airway inflammation (wall area percent, WAP), end-expiratory air trapping, suggestive of distal airway obstruction (expiratory to inspiratory mean lung attenuation ratio, MLAEI), and emphysema (percentage of lung volume with attenuation below - 950 HU, LAV%). The comparison groups in multinomial logistic regression models were participants with consistently normal spirometries, and participants with stable fixed obstruction (COPD). RESULTS: Compared to normal spirometry participants, and after adjusting for age, sex, race/ethnicity, BMI, smoking, and early arrival at the WTC disaster site, low FVC participants had higher WAP (ORadj 1.24, 95% CI 1.06, 1.45, per 5% unit), suggestive of proximal airway inflammation, but did not differ in MLAEI, or LAV%. COPD participants did not differ in WAP with the low FVC ones and were more likely to have higher MLAEI or LAV% than the other two subgroups. DISCUSSION: WTC workers with spirometric low FVC have higher QCT-measured WAP compared to those with normal spirometries, but did not differ in distal airway and emphysema measurements, independently of obesity, smoking, and other covariates.