Association between Spirometric Parameters and Depressive Symptoms in New Mexico Uranium Workers

Shiva Sharma MD, MPH¹

Xin W. Shore MS²

Satyajit Mohite MD, MPH³

Orrin Myers PhD²

Denece Kesler MD, MPH¹

Kevin Vlahovich MD, MS¹

Akshay Sood MD, MPH⁴

¹Preventive Medicine Section, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM USA

²Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque, NM USA

³Department of Behavioral Health, Psychiatry & Psychology, Mayo Clinic Health System, Mankato, MN USA

⁴Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM USA

Abstract

Background: Uranium workers are at risk of developing lung disease, characterized by low forced expiratory volume in one second (FEV1) and/or forced vital capacity (FVC). Previous studies have found an association between decreased lung function and depressive symptoms in patients with pulmonary pathologies, but this association has not been well examined in occupational cohorts, especially uranium workers.

Methods: This cross-sectional study evaluated the association between spirometric measures and depressive symptoms in a sample of elderly former uranium workers screened by the New Mexico Radiation Exposure Screening & Education Program (NM-RESEP). Race- and ethnicity-specific reference equations were used to determine predicted spirometric indices (predictor variable). At least one depressive symptom [depressed mood and/or anhedonia, as determined by a modified Patient Health Questionnaire-2 (PHQ-2)], was the outcome variables. Chi-square tests and multivariable logistic regression models were used for statistical analyses.

Results: At least one depressive symptom was self-reported by 7.6% of uranium workers. Depressed mood was reported over twice as much as anhedonia (7.2% versus 3.3%). Abnormal FVC was associated with at least one depressive symptom after adjustment for covariates. There was no significant interaction between race/ethnicity and spirometric indices on depressive symptoms.

Conclusions: Although depressive symptoms are uncommonly reported in uranium workers, they are an important comorbidity due to their overall clinical impact. Abnormal FVC was associated with depressive symptoms. Race/ethnicity was not found to be an effect modifier for the association between abnormal FVC and depressive symptoms. To better understand the mechanism underlying this association and determine if a causal relationship exists between spirometric indices and depressive symptoms in occupational populations at risk for developing lung disease, larger longitudinal studies are required. We recommend screening for depressive symptoms for current and former uranium workers as part of routine health surveillance of this occupational cohort. Such screening may help overcome workers’ reluctance to self-report and seek treatment for depression and may avoid negative consequences to health and safety from missed diagnoses.

Introduction

Uranium workers are at risk of pulmonary injury via two primary mechanisms: inhalation of radon daughters causing radiation-induced lung damage (1,2) and dust inhalation (3). Exposed workers are additionally at risk for developing cardiovascular pathology (4). Lung diseases can result in a clinically significant decline in pulmonary function and have been associated with various neuropsychiatric sequelae (5,6). Screening for and treatment of depression in interstitial lung disease (ILD) has been proposed to improve quality of life (6-8). Significant levels of depressive symptoms are described in patients with silicosis (8) and may adversely affect quality of life (9). In a study of patients with ILD, depressive symptoms correlate with dyspnea, forced vital capacity (FVC), sleep quality, and pain (7).

Presence of depressed mood or anhedonia, which is a significant decrease in deriving pleasure from the majority of one’s daily activities, on most days, is requisite for diagnosis of major depressive disorder (10). Individual inquiry of depressed mood has demonstrated 85-90% sensitivity for detection of depression; and addition of another question, specific for anhedonia, raises overall sensitivity to 95% for the two-question inquiry (11).

Our objective was to evaluate the prevalence of depressive symptoms in uranium workers, to examine their association with spirometric values, and examine race/ethnicity interaction with spirometry on depressive symptoms. We studied uranium workers enrolled in the New Mexico Radiation Exposure Screening and Education Program (NM-RESEP). New Mexico workers have been significantly impacted by uranium extraction activities and many are compensated through the Radiation Exposure Compensation Act (RECA) (12). The findings from this study may help elucidate the biopsychosocial impact of uranium-related lung abnormalities in New Mexico workers.

Methods

Study Design:

This is a cross-sectional analysis of baseline evaluation data from former New Mexico uranium workers (i.e., miners, millers, and ore transporters) voluntarily enrolled between 2004 and 2017 in NM-RESEP, a federally-funded health-screening and education program, located at the University of New Mexico (UNM) Health Sciences Center, serving Albuquerque and surrounding communities.

Data Collection:

Data were obtained from a self-reported questionnaire administered by a trained interviewer and confirmed by a physician/nurse practitioner. The questionnaire included demographics, severity of dyspnea via the modified Medical Research Council (mMRC) Dyspnea Scale (13), information on smoking history, cardiovascular status, and screening for depressive symptoms (using the modified Patient Health Questionnaire or PHQ-2) which includes two items on depressed mood and anhedonia (14). Body mass index (BMI) was calculated using measured height and weight. A prebronchodilator spirometry was obtained by trained technicians, utilizing standard guidelines from the American Thoracic Society and the European Respiratory Society (15). Test results were independently reviewed for quality by a pulmonologist. Gender- and race/ethnicity- specific reference equations were used to determine predicted normative values for spirometry (16). Abnormal values were defined by the lower limit of normal obtained from reference standards. Data was entered into a secure web-based Research Electronic Data Capture (REDCap) database.

Predictor and Outcome Variables:

The outcome included a positive response for PHQ-2 item on either depressive symptom, i.e., depressed mood or anhedonia. Predictor variables included spirometric parameters and race/ethnicity, including the absolute and percent-predicted values for FVC), forced expiratory volume in one second (FEV1), and the absolute value of the FEV1/FVC ratio. Lower limits of normal obtained from the reference standards from the Third National Health and Nutrition Examination Survey (NHANES III) were used to define abnormal spirometric values (16).

Statistical Methods:

Frequencies, percentages, means, and standard deviations in a univariate analysis were reported. For the purpose of analyses, the outcome variable was endorsement of either depressive symptom. Chi-Square tests were used to analyze categorical outcome variables and generate p-values to determine significance of the findings. In the multivariable logistic regression analysis, variables that were evaluated for potential confounding included smoking status and pack-years.

Ethical Approval and Funding:

This study was approved by the UNM Institutional Review Board or Human Resources Protections Office (14-058). The study was supported by NM-RESEP, which is funded by the Health Resources Services Administration (HRSA), and UNM Health Science Center CTSC Grant Number: UL1TR001449.

Results

Subject characteristics are shown in Table 1. Of the 570 uranium workers, 97.1% were men, 66.7% were of racial/ethnic minority with the largest group being American Indian (36.6%). Most workers were older (mean age of 68.5 ± 8.1 years) with BMI values in the overweight or obese categories (82.1%). 7.6% of workers reported at least one depressive symptom, with 7.2% and 3.3% reporting depressed mood and anhedonia, respectively. The prevalence of at least one depressive symptom in Hispanic, American Indian, and non-Hispanic White workers were 11.4%, 7.2%, and 4.1%, respectively (p=0.14 for all race/ethnicity group comparison) and post-hoc comparison between Hispanic and non-Hispanic White workers was significant (p=0.001) (not shown in Table 1). 66.9% of workers were either former or current smokers. With regards to previous pulmonary history, 15.3% and 10.0% of workers reported positive history of COPD and asthma, respectively.

Table 1. NM-RESEP Uranium Workers (2004-2017).

Both unadjusted univariate and adjusted multivariable analyses revealed that workers with abnormal FVC were at least 2.9 times more likely to endorse at least one depressive symptom. No associations were found between abnormal FEV1 or abnormal FEV1/FVC ratios and depressive symptoms (Table 2).

Table 2. Unadjusted and Adjusted Associations of the Presence of Depressive Symptoms on Spirometric Indices.

*Covariates in the above multivariable model using logistic regression analysis included: smoking status and smoking pack-years. **Further adjustment for the following covariates: age, gender, and race/ethnicity did not change results in the multivariable model (FVC OR: 2.86, 95% CI: 1.18-6.96, p=0.02).

Although the associations between spirometric indices and depressive symptoms appeared stronger among Hispanic workers than other race/ethnicity subgroups, this was not borne by a formal test of interaction between race/ethnicity and spirometric indices on either depressive symptom. However, interaction testing identified a trend towards significance for Hispanic workers between abnormal FEV1 and self-reporting of depressive symptoms (p=0.07) (Table 3).

Table 3: Interaction between Spirometric Indices and Race/Ethnicity on Depressive Symptoms.

*Logistic regression analysis was used.

Discussion

A minority of uranium workers sampled in this secondary analysis self-reported at least one depressive symptom (7.6%). Depressed mood was reported over twice as much as anhedonia was reported (7.2% vs 3.3%). Abnormal FVC on spirometry was found to be associated with depressive symptoms after adjustment for covariates. There was no significant interaction between race/ethnicity and spirometric indices on depressive symptoms.

Uranium ore extraction in New Mexico occurs in open pit or underground mines. Subsequently, uranium is isolated from ore via milling or heap leaching (17). Most of the workers in this study were subjected to hazardous working conditions marked by lack of provision of personal protective equipment (including respirators) to handle uranium and inhalational dust exposure. Inadequate ventilation in underground mines also led to increased radon and dust exposure and workers were not adequately informed of these occupational exposures by mining companies or federal agencies (i.e. US Atomic Energy Commission, Nuclear Regulatory Commission, US Department of Energy) (12).

Uranium enters the human body primarily via inhalation and ingestion (18). It deposits primarily in the lungs and skeleton (insoluble uranium) and kidneys (soluble uranium) (19) where it causes chemical and radiological damage to these organs (20). In a murine study, uranium was found to enter the central nervous system, crossing the blood-brain barrier and accumulating in the hippocampus, resulting in detrimental neurophysiological effects and changes in REM sleep patterns (21). A case study involving 81 American Indian uranium workers found anxiety and depression to be the most common mental health problems, and respiratory complaints and skin rashes were the most common physical health issues (22). Radon gas, a byproduct of the uranium decay process, attaches to dust particles and when inhaled into the lungs the alpha radiation released by radon daughters damages lung tissue. Like non-uranium industry workers engaged in other types of mining-related activities, uranium workers are at risk for occupational pneumoconiosis, presenting with features similar to silicosis (23), and chronic fibrotic ILD (3). Pneumoconiosis has been associated with increased risk of other pulmonary conditions, including pulmonary emboli (24), lung carcinoma (23), chronic obstructive pulmonary disease (COPD) (26), tuberculosis (27), and clinically significant decline in lung function (28).

Many chronic pulmonary conditions such as asthma, COPD (29), bronchiectasis (30), and lung cancer (31) are associated with depressive symptoms. In a prospective study of patients with bronchiectasis, low FEV1 values were observed among patients with depressive symptoms (30). In a study of French dairy farmers, Guillien (32) found depression was associated with lower FEV1. A 2013 systematic review and meta-analysis revealed that the relationship between COPD and depression is bidirectional (33). Our study did not contain information regarding history of a prior or current diagnosis of depression for enrolled patients, thus our secondary analysis is not a like-for-like comparison to existing literature on this topic. Our study involved individuals with mostly normal lung function, indicating that the association between abnormal FVC and depressive symptoms may be seen relatively early in the disease course.

Psychosocial factors may play a role in the development of workplace-associated disability in workers with respiratory impairment, but evidence-based guidance to address these psychosocial factors is limited (34). The low prevalence of depressive symptoms in our study may reflect the high proportion of men enrolled (97.1%), as overall prevalence of depression in men is approximately half that of women (35). Alternatively, men may under-report due to a lack of awareness and understanding of depression and fear of stigmatization for self-reporting amongst coworkers or wider society. Additionally, use of the standard PHQ-2 and DSM diagnostic criteria in American Indians may not produce reliable results due to potential cultural and linguistic differences (36). The rate of depression in American indigenous populations has found to be 8.9% (which is higher than all other racial/ethnic groups except biracial individuals) and can range from 10-30% (37), however, the prevalence of depressive symptoms in American Indian workers in our study was 7.2%. To the best of our knowledge, no validation studies have been performed for use of any version of the PHQ-2 in New Mexican American Indian populations. The PHQ-2 has been validated in English- and Spanish-speaking Hispanic Americans (38). Perini found ethnic minorities diagnosed with “chronic nonspecific lung disease” exhibited higher absolute prevalence of depressive symptoms than the ethnic majority (29). Our study findings partially agree with Perini’s findings in that Hispanic uranium workers were more likely to endorse depressed mood than non-Hispanic White workers.

Our study was a cross-sectional, secondary analysis of an occupational cohort of mostly elderly, former uranium workers enrolled in NM-RESEP. Longitudinal analysis of this association may further elucidate the direction of the association. Our study could benefit from culture-specific depression diagnostic criteria paired with spirometric measures to specific pulmonary diagnoses. While anhedonia has customarily been associated with loss of pleasure (10), the construct has recently expanded to include interest in activity, effort, and discrimination between anticipation and consummatory forms of pleasure. New approaches for anhedonia assessment are in development (39). Our assessment of anhedonia may have been limited and a more robust screening tool that screens for additional depressive symptoms beyond depressed mood and anhedonia, such as the PHQ-9 or Hospital Anxiety and Depression Scale (HADS) rather than the PHQ-2, could improve result validity. As depression has a complex nature, a more rigorous biopsychosocial assessment would help in determining the role pulmonary pathology plays in depression in this study sample. To the best of our knowledge, this is the first study to examine the association of spirometric indices with depressive symptoms in former uranium workers. The strengths of our study include the robust participation of minority workers due to use of a mobile screening unit, its clinical relevance in light of ongoing uranium-associated activity, and potential future impact on health. Further study on this topic is merited as untreated depression in workers poses potential risks to workplace safety. As industrial use of nuclear material continues in the United States and other countries such as Kazakhstan, Canada, and Australia, this area of study is relevant to occupational health on a global scale. We recommend screening for depressive symptoms in current and former uranium workers as part of routine health surveillance to better address reluctance to self-report and seek treatment for depression, as well as to avoid potential negative consequences to health and safety from a missed diagnosis.

Acknowledgments

Guarantor: Akshay Sood MD, MPH takes responsibility for the content of the manuscript, including the data and analysis.

Author contributions: All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors contributed substantially to the data analysis and interpretation and the writing of the manuscript.

Financial/non-financial disclosures: All authors report no conflict of interest.

Abbreviation List

• BMI: body mass index
• COPD: chronic obstructive pulmonary disease
• CTSC: Clinical and Translational Science Center
• DSM: Diagnostic and Statistical Manual of Mental Disorders
• FEV1: forced expiratory volume in one second
• FVC: forced vital capacity
• HADS: Hospital Anxiety and Depression Scale
• ILD: interstitial lung disease
• mMRC: modified Medical Research Council
• NHANES III: The Third National Health and Nutrition Examination Survey
• NM-RESEP: New Mexico Radiation Exposure Screening and Education Program
• PHQ-2/PHQ-9: Patient Health Questionnaire-2/Patient Health Questionnaire-9
• RECA: Radiation Exposure Compensation Act
• REDCap: Research Electronic Data Capture
• UNM: University of New Mexico

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Cite as: Sharma S, Shore XW, Mohite S, Myers O, Kesler D, Vlahovich K, Sood A. Association between Spirometric Parameters and Depressive Symptoms in New Mexico Uranium Workers. Southwest J Pulm Crit Care. 2021;21(2):58-68. doi: https://doi.org/10.13175/swjpcc015-20 PDF 

A Population-Based Feasibility Study of Occupation and Thoracic Malignancies in New Mexico

Claire R. Pestak, MPH ^1,2

Tawny W. Boyce, MS, MPH ¹

Orrin B. Myers, PhD ⁴

L. Olivia Hopkins^, MD ³

Charles L. Wiggins, PhD ^1,2,3

Bruce R. Wissore, JD, PhD, MA, MS, MS ^3,6

Akshay Sood, MPH, MD ^3,5

Linda S. Cook, PhD ^1,3

¹UNM Comprehensive Cancer Center, University of New Mexico, MSC 07-4025,
1 UNM, Albuquerque, NM, 87131, USA

²New Mexico Tumor Registry, University of New Mexico, MSC 11 6020, 1 UNM, Albuquerque, NM, 87131, USA

³Department of Internal Medicine, University of New Mexico School of Medicine, MSC 10 5550, 1 UNM, Albuquerque, NM, 87131, USA

⁴Department of Family and Community Medicine, University of New Mexico School of Medicine, MSC 09-5040, 1 UNM, Albuquerque, NM, 87131, USA

⁵Miners Colfax Medical Center, Raton, NM, 87740, USA

⁶Southwestern Illinois College, Belleville, IL, 62221, USA

Abstract

Background

Occupational exposures in mining and oil/gas extraction are known risk factors for thoracic malignancies (TMs). Given the relatively high proportion of these industries in New Mexico (NM), we conducted a feasibility study of adult lifetime occupational history among TM cases. We hypothesized a higher proportion of occupational TM in NM relative to the estimated national average of 10-14%.

Methods

We identified incident TM cases through the population-based New Mexico Tumor Registry (NMTR), from 2017- 2018. Cases completed a telephone interview. An adjudication panel reviewed case histories and classified cancers as probable, possible, or non-occupational related, taking into account the presence, duration, and latency of exposures. We characterized recruitment and describe job titles and exposures among those with occupational TMs. We also compared the distributions of industry between those with and without occupational TM.

Results

The NMTR identified 400 eligible TM cases, 290 of which were available to be recruited (n=285 lung/bronchial cancer; n=5 mesotheliomas). Of the latter, 60% refused and 18% were deceased, 9% had invalid addresses, 11% were unable to be reached by telephone, and 3% were too ill to participate. The 43 cases who completed an interview held 236 jobs. A total of 33% of cases were classified as probable occupational TM and 5% as possible occupational TM.

Conclusions

High rates of early mortality and refusals were significant barriers to study participation. Nonetheless, the proportion of probable occupational TMs greatly exceeded the estimated national average, highlighting the need for further study of occupational TM in the state.

Editor's Note: See The Best Laid Plans of Mice and Men for accompanying editorial.

Introduction

Lung cancer and mesothelioma are the most common thoracic malignancies (TMs). Lung cancer is the second most common cancer in the United States (US) and in New Mexico (NM) and the leading cause of cancer death (1). Mesothelioma is relatively rare but has a specific association with occupational exposure to asbestos. For this paper, lung cancer and pleural mesotheliomas are combined as TMs. Despite some treatment advances (2,3), five-year relative survival is less than 20% for all TM (4).

The strongest risk factor for lung cancer is cigarette smoking (5). Other established risk factors for TMs include exposure to asbestos, uranium, radon gas, and other cancer-causing agents in the workplace, radiation therapy to the lungs, and a family history of lung cancer (6-8). The importance of occupation in TMs is emphasized by the Global Burden of Disease (GBD) report indicating that the two main cancers caused by occupational exposures worldwide were lung cancer (274,000 deaths annually) and mesothelioma (27,000 deaths annually) (9). Various estimates attributing occupation to lung cancer include: a 1981 US estimate of 15% for men and 5% for women, or 10% overall (10), a 1987 NM estimate of 14% in men (11); and, a 2003 US estimate for deaths of 8.0%–19.2% for men and 2% for females, or 6.3%-13.0% overall (12,13). Thus we estimated that overall in the US, 10%-14% of TMs could be attributable to occupation.

Historic and current occupational exposures are of particular interest in NM. Mining, in particular uranium mining, was a major operation in NM from 1950-1970. Mining is still an important industry in this region: between 2011 and 2015, the NM mining industry saw a 20% increase in employment for all types of mining (14). NM also has significant employment in the Mining, Quarrying, and Oil and Gas Extraction industry relative to other parts of the Southwest (15). These industries have a greater share of local employment in NM than in the US overall (16). Additionally, NM was the ninth highest natural gas producer in the US in 2018, producing 1.49 million cubic feet of natural gas (17).

Given the historic and current extraction activities in NM, we hypothesized that NM would have a higher proportion of occupational TMs than the estimated national average of 10%-14%. As an initial step in estimating this occupational TM cancer burden in NM, we conducted a feasibility study to obtain adult lifetime occupational histories for TM cases.

Methods

Recruitment and Data Collection 

This feasibility study was approved (#16-306) by the Human Research Review Committee at the University of New Mexico and cases provided signed, informed consent. We identified incident TM cases from February 1, 2017 to February 2, 2018 via the population-based New Mexico Tumor Registry (NMTR), a founding member of the National Cancer Institute’s (NCI) Surveillance Epidemiology and End Results (SEER) Program. Cases were identified by two methods: (1) rapid case ascertainment (RCA) via electronic pathology reports and (2) usual case ascertainment (UCA) via tumor registrars manually collecting data from around the state. Contact with eligible cases involved a three-step process. In step 1, the NMTR contacted treating physicians explaining the study and advising them of their patient’s eligibility allowing the physician to state any objection to patient contact. In step 2, the NMTR contacted the patient (letter and study brochure in English and Spanish) informing them about the study and allowing them to opt-out from further contact. In the special case of no physician of record, patients were contacted after a three month wait period. Patients who refused participation or were deceased were ineligible for study contact. In step 3, for the remainder, contact information was released to study personnel.

All potential cases in step 3 were mailed documents in both English and Spanish including: an introductory letter, a flyer about benefits counseling, a Frequently Asked Questions sheet, two copies of a Residence and Work History worksheet, a Life Events Calendar, showcards, and two copies of the consent form. One consent form was for the case to sign and keep and the other was signed and returned to the study, along with one copy of the Residence and Work History worksheet. Showcards functioned as a visual aid by listing possible answers to interview questions. The Life Events Calendar functioned as a memory aid to anchor major life events like marriages, births, deaths, relocations, job changes, and other historical events. The Residence and Work History Worksheet gave the cases a time frame to date their paid jobs and occupations, held for at least 6 months, during their adult life and was used for reference during the interview. Work did not have to occur in the state of NM. Study interviewers contacted cases by telephone to answer questions. Those who expressed a willingness to participate were asked to complete and return the worksheets/consent form and to schedule an interview.

Consenting cases completed the same structured telephone interview with an embedded script that obtained information on demographics, lifestyle factors, medical history, reproductive history (women only) and adult lifetime occupational history. For each and every job held for six months or longer from age 18 years onwards, the cases provided job title, city and country of job location, job status (full-time/part-time), job duties, exposure information on relevant agents (18) (a list of more than 30 relevant exposures was provided to cases) including the duration of each exposure, and age at start and end of the job. All cases were asked all job-related questions providing a detailed and specific work history for each individual. Data were recorded in Research Electronic Data Capture (REDCap) database (19). Cases received a small merchandise card in appreciation. All potential cases and surviving family members were given an optional referral to a benefits counselor regardless of their self-reported exposures or determination by the Data Adjudication Committee (DAC).

Determination of Occupational TM

De-identified occupational history summaries were reviewed by the DAC to determine if each case was attributable to occupational exposures, as summarized below. The DAC was composed of three voting members: a pulmonologist with expertise in occupational pulmonary diseases associated with the coal and uranium mining industries; a preventive medicine specialist with expertise in occupational health who works in the Center for Occupational Environmental Health Promotion; and, an attorney with expertise in the medicolegal definitions for causation in the occupational setting. A non-voting member (CRP) served as the committee Chair to tally votes and mediate further discussion if necessary.

This expert panel independently reviewed the de-identified individual job histories for each case, and considered exposures that had a latency of at least 10 years, exposure durations of at least one year, and exposure intensity through self-reported frequency of exposure on the job. To aid in assessment, each panel member was provided a summary table of the known strength of the association between relevant exposures and TM occurrence (available upon request) (20-27). After independent review, the panel would meet to discuss and vote on classification. If all three DAC members found sufficient evidence for relevant occupational exposure, the case was classified as a probable occupational TM. If at least one DAC member found insufficient evidence for relevant occupational exposure, the case was classified as a possible occupational TM. If all DAC members found insufficient evidence for relevant occupational exposure, the case was classified as non-occupational TM. Smoking history for each case was provided to the DAC, but occupational cancer was decided independent of smoking, except in the case of asbestos exposure where a synergistic relationship is well supported by the published literature (28). Because of the participant burden and the high likelihood of misclassification, we did not collect information on environmental tobacco smoke or biomass/coal smoke for each job reported in this study. A letter was sent to each case with the DAC’s determination.

Analysis

After the determination of occupational TM status by the DAC, each job title for each case was coded to an industry using the NIOSH Industry and Occupation Computerized Coding System (NIOCCS) (29). Each job title was submitted, and using the "Census 2010/NAICS 2007/SOC 2010" coding scheme, the most appropriate 2010 Industry Census Code provided by the industry and occupation output was selected. If the industry was unclear based on the job title alone, the work history was reviewed for the company name, job duties, or other relevant notes. In these situations, once an industry was selected, the industry was independently verified by another study team member. The possible 269 industry categories in the 2010 census system were further summarized into 20 North American Industry Classification System (NAICS) sectors (30).

Results

Of the 400 eligible cases initially identified via the NMTR, 110 (28%) were not released to study personnel for the following reasons: 33 (30%) refused to have their information released to investigators; 47 (43%) were deceased; 23 (21%) had no physician of record and were in the 3-month wait period; four (4%) had an invalid address; two (2%) were subsequently determined to be ineligible, and one case (1%) was determined to have a duplicate record in the NMTR. The remaining 290 eligible cases were invited to join the study, of which 285 had lung cancer and 5 had mesothelioma. Over-all, refusals (60%) and deaths (18%) were the two major reasons for non-participation in the interview, but cases also had invalid addresses (9%), were unable to be reached by telephone (11%), or were too ill to participate (3%). Of the 43 cases, 98% agreed to future tumor tissue testing and medical record reviews.

Demographic characteristics of cases are detailed in Table I.

Table I. Demographics of Thoracic Malignancies (TM) cases

Among the cases, 51% were women, 70% were Non-Hispanic White, 86% were >60 years of age, 19% reported a parent had lung cancer. In terms of insurance and benefits, 95% had some type of health insurance, but only 9% had sought compensation through Social Security Disability, Worker's Compensation, or the Veterans Administration before the study. Medical Histories of cases are detailed in Table II.

Table II. Medical History of Thoracic Malignancies (TM) cases.

Among the cases, 49% were overweight/obese. Both smoking (72% current/former cigarette smokers) and non-malignant respiratory diseases (40% reporting pulmonary fibrosis, COPD, or chronic bronchitis) were common.

Cases reported 236 jobs representing 20 NAICS sectors, and 14 (33%) were classified as probable and 2 (5%) as possible occupational TM. Among the probable occupational TM cases, 11 (79%) were men, and both the possible occupational TMs were men. The 14 cases with a probable occupational TM self-reported one or more of the following occupational exposures: aluminum production (n=1), arsenic (n=1), asbestos (n=7), cadmium (n=1), coal-tar (n=1), diesel (n=7), ether (n=5), nickel (n=2), paint (n=1), radiation (n=1), silica (n=9), and soot (n=2). The joint distribution of these cases by job title and exposure category is shown in Figure 1.

Figure 1. Relevant Self-Reported Exposures by Job Titles per Industry Sector for the Cases with Occupationally Related Thoracic Malignancies*

*Exposures deemed to be causal by the Data Adjudication Committee.

The study population only included those who were diagnosed and captured by the NMTR from February 1, 2017 to February 2, 2018 (n=400). Case identification at the NMTR, especially for cancers like TMs where there may not be a pathology report, may be ascertained more than a year after diagnosis. A NMTR query in March 2020 for diagnoses in the same time period noted above yielded more than double the number of TM cases (n=913). Thus we had the opportunity to compare those identified early (n=400) and up to two years later (n=513) as well as those released to the study for contact (n=290) with those whose names were not released for study contact (n=110) by selected demographic and histological characteristics (Table III).

Table III. Summary of the characteristics of the lung cancer and mesothelioma cases diagnosed between 2/1/17 – 2/2/18 for the OCTOPUS Study. Data source New Mexico Tumor Registry (NMTR).

There were differences in age between the 400 cases identified during the study period (50% for those 70 years and older) and the 513 cases identified later (57% for those 70 years and older) (p<0.05) and rurality between the 400 cases identified during the study period (23% rural) and the 513 cases identified later (44% rural) (p<0.001). Apart from the obvious difference in death as this was a criteria for not releasing contact to the study, a difference in histology was noted for those released to the study (77% non-small cell carcinoma) and those not released (66% non-small cell carcinoma) (p<0.05).

Discussion

This feasibility study was designed to obtain lifetime occupational histories from a population-based sample of TM cases and to determine the proportion of such cases that were likely attributable to occupational exposures. Despite our efforts to recruit these subjects in a timely manner, high rates of early mortality and refusals were significant barriers to study enrollment, indicating that a definitive study is not possible based on these methods. Among those who participated in the study, the proportion of cases with occupational TM (33%) was two to three times higher than prevailing national estimates (10-14%). While this result is intriguing and may warrant further study, we cannot say with certainty if this result is due to the low response percentage and the possible selection bias of having cases that were more likely to have relevant occupational exposures, or if this result truly reflects the occupational exposures in NM.

Recruiting TM cases via a population-based cancer registry is challenging. In total, 25% of eligible cases died before they could be recruited to the study via the NMTR or study personnel. An even higher proportion refused, 52% of eligible cases, in part due to poor health as cancer progressed and to the burden of treatment concurrent with study participation. Such a high refusal percentage could be a source of selection bias in which various occupations were under- or over-represented, but we had no data to address this bias directly. Additionally, the study only included those who were diagnosed and captured by the NMTR from February 1, 2017 to February 2, 2018 (n=400). We noted a substantial difference in rurality between the 400 cases identified for our study (23% rural) and the 513 cases identified later (44% rural). The majority of counties in NM are rural or frontier (26/33) (31). TM cases diagnosed among residents of these areas are less likely to receive health care in facilities that are served by pathology laboratories with electronic reporting; instead cancer registrars visit the facilities to manually abstract medical records leading to a longer reporting timeline. These results imply that rural TM cases were under-represented in our study, and since those with mining and other extraction occupations are more likely to reside and get health care in rural areas, our estimate of 33% occupational TM might be an underestimate.

From the list of more than 30 possible exposures that are known or suspected carcinogens for lung cancer (32), probable occupational TM cases reported exposures to aluminum production, arsenic, asbestos, cadmium, coal-tar, diesel fumes, ether, nickel, paint, radiation, silica, and soot. Limitations of these results include the difficulty of retrospective estimation of the intensity and duration of each of these exposures at each job, and the fact that the study did not have enough cases to conduct an analysis accounting for other exposures such as tobacco use, comorbidities, and socioeconomic factors (33). Further, we did not have information on exposures to indoor smoke in the home from, for example, wood burning stoves.

The U.S. does not have a comprehensive employment and exposure database or an occupational disease mortality surveillance system that could provide more objective and comprehensive occupational information than self-report. In some countries, researchers can link data from national cancer registries and occupational databases to help confirm associations between occupational exposures and cancers (34). Inclusion of an occupational history in medical records could also provide more objective data, but such practices are currently sporadic and non-uniform. While death certificates often record a decedent’s longest or lifetime occupation, no exposure details are included, and access to this minimal data is often restricted in an effort to maintain confidentiality (35). Thus, improvements to the evaluation of occupation and occupational exposures for cancers such as TMs on a population-basis remains a challenge.

Other strengths of our study not indicated above include: our success in ascertaining a detailed adult lifetime occupational history from lung cancer survivors using an English or Spanish interview; inclusion of racial/ethnic minorities; inclusion of both men and women (with 21% of women in our study having a probable occupational TM); no eligibility restriction to a specific industry or exposure; a rigorous procedure via the DAC to establish a probable-occupational, possible-occupational, or non-occupational classification for each case; and offering cases a referral for benefits counseling (65% accepted). The limitations of this study have been discussed above.

This feasibility study suggests that 33% of cases had a probable occupational TM, two to three times the national historical estimate, highlighting the importance of exposures and jobs in the NM population that can lead to occupational TMs. However, a more definitive study is not feasible based on the methods used in this study as the ability to overcome the above-described methodological and recruitment challenges remains a significant barrier to further population-based studies of occupation-related TM in NM and the US.

Acknowledgements: This research utilized the UNM Comprehensive Cancer Center (UNMCCC) Biostatistics Shared Resource, and the UNM Clinical & Translational Science Center, the Surveillance, Epidemiology and End Results Program (SEER) data for New Mexico, and REDCap (DHHS/NIH/NCRR #8UL1TR000041).

Funding: The grant sponsor was the UNM Foundation, a non-profit corporation, organized exclusively for charitable and educational purposes under Section 501(c)(3). CRP, TWB, and LSC and the Biostatistics Shared Resource received support from the UNM Comprehensive Cancer Center (NCI P30 CA118100). CRP and CLW received support by Contract HHSN261201800014I, Task Order HHSN26100001 from the National Cancer Institute.

Institution and Ethics approval and informed consent: The work was performed at the University of New Mexico and the Human Research Review Committee (Federal wide Assurance FWA00003255) approved this study. Study participants provided written informed consent.

Acknowledgements: This research utilized the UNM Comprehensive Cancer Center (UNMCCC) Biostatistics Shared Resource, and the UNM Clinical & Translational Science Center, the Surveillance, Epidemiology and End Results Program (SEER) data for New Mexico, and REDCap (DHHS/NIH/NCRR #8UL1TR000041).

Funding: The grant sponsor was the UNM Foundation, a non-profit corporation, organized exclusively for charitable and educational purposes under Section 501(c)(3). CRP, TWB, and LSC and the Biostatistics Shared Resource received support from the UNM Comprehensive Cancer Center (NCI P30 CA118100). CRP and CLW received support by Contract HHSN261201800014I, Task Order HHSN26100001 from the National Cancer Institute.

Institution and Ethics approval and informed consent: The work was performed at the University of New Mexico and the Human Research Review Committee (Federal wide Assurance FWA00003255) approved this study. Study participants provided written informed consent.

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Cite as: Pestak CR, Boyce TW, Myers OB, Hopkins LO, Wiggins CL, Wissore BR, Sood A, Cook LS. A Population-Based Feasibility Study of Occupation and Thoracic Malignancies in New Mexico. Southwest J Pulm Crit Care. 2021;22(1):23-35. doi: https://doi.org/10.13175/swjpcc057-20 PDF 

Adjunctive Effects of Oral Steroids Along with Anti-Tuberculosis Drugs in the Management of Cervical Lymph Node Tuberculosis

Adjunctive Effects of Oral Steroids Along with Anti-Tuberculosis Drugs in the Management of Cervical Lymph Node Tuberculosis

Babulal Bansiwal¹

Maneesha Jelia²

Ramesh Chand Meena²

Satyam Agarwal²

Shinu A²

Departments of ¹Respiratory Medicine and ²Anatomy

Government Medical College, Kota

Rajasthan 324010, India

Abstract

Background: Tuberculosis (TB) can infect both pulmonary and extra-pulmonary organs. In India pulmonary TB accounts for 80% of cases and extrapulmonary TB (EPTB) accounts for 20% cases. Cervical lymph nodes are the most location for EPTB.

Aims and Objectives: To study the efficacy of treatment with oral steroids along with anti-tuberculosis treatment in cervical lymph node tuberculosis.

Methods: A total of 60 patients were enrolled in the study all with EPTB and cervical lymphadenitis. These 60 study patients were randomised into two groups. Group-I consisted of 30 patients given anti-tuberculosis therapy along with prednisolone 1mg/kg body weight for 4 weeks followed by tapering at 0.5 mg/kg body weight over 4 weeks. Group-II was comprised of 30 patients given antituberculosis treatment plus placebo

Results: After completion of treatment 27 patients in Group 1 (90%) showed complete resolution and 3 patients (10%) had residual evidence of lymphadenitis with no change. In contrast, only 19 patients (63.3%) showed complete resolution in Group 2 and 11 patients (36.7%) had residual lymphadenitis present (10 had no change, 1 had increase in size).

Conclusion: We conclude that steroids given with antituberculosis treatment to patients with cervical lymphadenitis led to faster and earlier resolution of tuberculous lymphadenitis.

Introduction

Tuberculosis (TB) is an ancient disease that affects both pulmonary and extra-pulmonary organs. In India most TB cases are pulmonary (80%) but extrapulmonary TB (EPTB) accounts for a substantial proportion (20%) (1). Peripheral lymph node tuberculosis is observed in about 5% of all TB patients and 30-55% of extra-pulmonary TB cases (2). Cervical lymph nodes are the most common lymph nodes affected, classically termed as “scrofula”, although supraclavicular, axillary, inguinal nodes may also be involved (3-5). Lymphadenopathy may lead to complications by compression of adjacent structures, organs, and blood vessels or fistula formation (6-10). Multiple studies have shown better outcomes with addition of steroids to anti-tuberculosis treatment in extrapulmonary tuberculosis including pleural effusion, pericardial effusion, tubercular meningitis, and mediastinal lymphadenopathy (11,12). However, the safety and efficacy of this approach remains largely unproven except in cases of intrathoracic obstruction where it was found to relieve the pressure on the compressed bronchus (13).

Aims and Objectives

To study the efficacy of treatment with oral steroids along with anti-tuberculosis treatment in cervical lymph node tuberculosis.

Materials and Methods

Patients: Sixty patients with cervical lymph node tuberculosis seen from 1st October 2013 to 30^th September 2014 in the Department of Respiratory Medicine, Government Medical College, Kota, India participated in the study. All cases of cervical lymph node tuberculosis found to have cyto-pathological, histo-pathological, immunological and/or bacteriological evidence of TB and who had not received any anti- tuberculosis therapy in the past, were included in the study. Patients were excluded if they were pregnant or had a chronic disease such as diabetes mellitus, hypertension, peptic ulcer disease, alcoholism, or HIV-AIDS. Patients were also excluded if they had a detectable abscess.

Study Design: The study was an open label, randomized, prospective and placebo-controlled interventional study comparing the efficacy of the addition of two months treatment with oral corticosteroids along with Revised National Tuberculosis Control Programme (RNTCP) recommended anti-TB therapy.

Sixty patients were randomised into two groups by a computer-generated random table. All patients were given category I anti-tuberculosis therapy (ATT) consisting of INH 600 mg and rifampicin 450 mg daily for 6 months with pyrazinamide 1500 mg daily for the first 2 months. Group-I consisted of 30 patients given category I RNTCP-recommended therapy along with prednisolone 1mg/kg body weight for 4 weeks followed by tapering at 0.5mg/kg body weight for 4 weeks. Group-II was comprised of 30 patients given category I RNTCP-recommended therapy plus placebo.

All the study cases were monitored clinically by visits after 1, 2 and 6 months.

Statistical Analysis: Pearson’s x² test or Fisher’s exact test was used to evaluate correlations between categorical variables, as appropriate. Relationships among continuous variables was evaluated using Student’s t- test. All tests of significance are two-tailed, and p < 0.05 was considered to reflect significance.

Results

The patients were well matched between groups in age (27.5 + 12.9 years vs. 26.3 + 11.7 years, p=0.612) and sex (12M/18F vs. 11M/19F). The groups were well-matched in other clinical characteristics (Table 1).

Table 1. Clinical characteristics of patients at beginning of therapy.

In addition to the above, the patients were well-matched by the extent of both upper and lower lymphadenopathy (Group I, 25/30; Group 2, 28/30), absence of chest lesions (Group I, 1/30; Group 2, 2/30), and positive histopathology on needle aspiration (Group I, 27/30; Group 2, 26/30). Out of 26 patients of Group II, 4 (13.3%) patients were diagnosed by AFB smear of the needle aspirate as well as cytopathological examination, 2(6.7%) had only AFB smear positivity and 22 (86.7%) had only cytopathological confirmation. None had a positive sputum smear.

Most of the patients in Group-I had earlier lymph node resolution compared to Group-II (Table 2).

Table 2. Initial lymph node status and after varying durations of treatment.

This table shows the status of the lymph node initially and after varying duration of treatment. After completion of treatment 27 patients (90%) showed complete resolution and only 3 patients (10%) had no change in Group-I. In contrast, only 19 patients (63.3%) in Group-II showed complete resolution and 11 patients (36.7%) had residual lymph nodes (10 with no change, 1 with an increase in size). Most patients had a negative AFB smear from the needle aspirate after 6 months in both Group-I (27 patients) and group-II (26 patients).

Only 2 patients in Group-I (6.67%) had complications as compared to 09 (30.0%) in Group-II (p<0.001). The complications were in the form of abscess, sinus and/or new lymph node/s. All these patients needed surgical exploration during the course of treatment. Sequelae in form of residual lymph node was also higher in Group II patients (10 out of 30 patients) as compared to Group I (3 out of 30, p<0.001).

Overall, the incidence of side effects was greater in Group-II. This difference was mostly due to a higher occurrence of joints pain and skin rashes in Group-II than Group-I, (8 and 4 patients vs. 1 and 1 patients respectively).

Discussion

The present study was done to determine the role of steroids in the management of cervical lymph node tuberculosis. In contrast to 20 patients (66.67%) in the non-steroid group-II who had complete resolution after 6 months, 27 patients (90%) in the steroid group had complete resolution. Blaikely et al. (14) reported complete resolution in 82% of their non-steroid study patients which was similar to results of our study.

In the present clinical study, only 2 patients (6.66%) in the steroid group had complications as compared to 9 (30.0%) in the non-steroid group. The complications were in the form of abscess, sinus and/or new lymph node/s. In Group II, fresh lymph nodes appeared in 4, existing lymph node increased in 1, abscess formation occurred in 3 while 2 patients developed sinuses. Sequela in the form of residual lymph node was also higher in the non-steroid patients (10 out of 30, 33.33%) as compared to the steroid treated patients (3 out of 30 patients, 5%, p<0.001). Results were comparable to other studies (15).

We used a moderate dose of steroids for 2 months. The major concern against the use of steroids when given along with anti-TB treatment in tubercular lymphadenitis are adverse systemic effects. However, the overall incidence of side effects with anti-TB treatment were more in the non-steroid group in the form of joint pains and skin rashes, (8 and 4 patients v/s 1 and 1 patients respectively). Gastro-intestinal side effects i.e. nausea/vomiting and pain abdomen, were slightly higher in the steroid-treated patients.

Conclusion

We conclude that steroids when given along with anti-tubercular treatment led to faster and earlier resolution of tuberculous lymphadenitis. Complication and sequela in form of residual lymph node are also less in steroid group as compared to non-steroid group. It is unclear if long-term outcomes are affected. However, this data suggests that justification for routine use of corticosteroids could be made in tubercular cervical lymphadenitis.

References

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Cite as: Bansiwal B, Jelia M, Chand Meena RC, Agarwal S, A S. Adjunctive Effects of Oral Steroids Along with Anti-Tuberculosis Drugs in the Management of Cervical Lymph Node Tuberculosis. Southwest J Pulm Crit Care. 2021;22(1):16-20. doi: https://doi.org/10.13175/swjpcc067-20 PDF 

Respiratory Papillomatosis with Small Cell Carcinoma: Case Report and Brief Review

Priya Sharma

Anish Kumar

Bharath Janapati

Anil Kumar Jain

Department of Respiratory Medicine

National Institute of Tuberculosis and Respiratory Diseases

New Delhi 110030, India

Abstract

Respiratory Papillomatosis is a rare disease in which multiple exophytic squamous wart-like lesions occur within the respiratory tract. Recurrent Respiratory Papillomatosis (RRP) has the potential for malignant transformation to squamous lung cell carcinoma with a dismal prognosis. Most of the prior literature has shown malignant transformation of respiratory papillomatosis into squamous cell carcinoma. Here, we report a rare presentation of respiratory papillomatosis coexisting with small cell carcinoma and a review of relevant literature.

Introduction

RRP is a rare disease in which multiple exophytic squamous wart-like lesions occur within the respiratory tract. RRP has the potential for malignant transformation to squamous lung cell carcinoma with a dismal prognosis. The cases of squamous cell carcinomas developing within lung papillomas have been reported and these are usually associated with HPV 11 DNA (1,2). Here we present a rare case of respiratory papillomatosis coexisting with small cell carcinoma.  

Case Report

A 47-year-old woman presented with right sided chest pain and cough for 8 months. She had history of two episodes of blood streaked sputum four months ago. She also complained of loss of appetite and weight loss. She was a former smoker (1-2 cigarettes per day for 2-3 years quitting 5 years ago) and had a history of exposure to biomass fuel while working as a farmer. On examination pallor and clubbing was noted. Chest x-ray was suggestive of hilar enlargement (Figure 1).

Figure 1. Initial chest radiography.

Contrast-enhanced CT of the chest showed homogeneously enhancing soft tissue density central lung mass that is narrowing and circumferentially encasing right main bronchus. The mass was abutting arch of aorta and the ascending aorta and circumferentially encasing and narrowing the superior vena cava and right main pulmonary artery. Subsegmental collapse of superior segment of right lower lobe was also seen with right paratracheal and pretracheal lymph node enlargement (Figure 2).

Figure 2. Representative axial image from thoracic CT scan in soft tissue windows showing the right lung mass.

Flexible optic bronchoscopy showed an endoluminal irregular mass invading distal end of trachea along with carina and right main bronchus (Figure 3).

Figure 3. Photograph taken at bronchoscopy of the endobronchial mass in the distal trachea and right main bronchus.

Endobronchial biopsy showed papillary structures with fibro vascular cores lined with cell with moderate amount of cytoplasm with enlarged nuclei with granular chromatin and inconspicuous nuclei suggestive of RPR on histopathological examination. The patient was lost to follow up. Two months later she presented with increased breathlessness. Chest x-ray showed unilateral opaque right hemithorax with mediastinum slightly shifted to right (Figure 4).

Figure 4. Repeat chest radiography taken 2 months after initial presentation.

Hyponatremia was seen on routine blood investigation. CECT chest showed a well-defined heterogeneously enhancing soft tissue mass lesion with irregular margins involving the upper and middle lobe of right lung (Figure 5).

Figure 5. Coronal view of repeat thoracic CT in soft tissue windows.

The mass was encasing the right main bronchus and distal trachea, abutting large vessel, shifting trachea towards right side with moderate pleural effusion. Sputum analysis for acid-fast bacteria and malignant cells was negative. Ultrasound of abdomen showed no abnormality. Pleural fluid analysis showed paucicellular smear on cytology with ADA 20.5U/l, Protein 2.4 mg/dl and glucose 95.1 mg/dl. The patient refused bronchoscopy but consented to an ultrasound guided trans-thoracic biopsy. Histopathology showed pulmonary tissue with infiltrating tumor and the tumor was made up of sheets of small round cells with irregular contours suggestive of small cell carcinoma. Patient refused further management and left against medical advice. She passed away 11 days later.

Discussion

The incidence of RRP is bimodal, with the juvenile-onset form typically first occurring in children aged 2 to 4 years and adult-onset RRP typically occurring in adults aged 20 to 40 years. Juvenile-onset RRP is thought to be caused from peripartum exposure through an infected birth canal (3). Risk factors for adult-onset RRP include multiple lifetime sexual partners as well as a high frequency of oral sex. There was no statistically significant difference in illicit drug use between patients with adult-onset RRP vs a control group in a study by Ruiz et al. (4). RRP affects, from the most common site to the least common site, the true vocal cord, oral cavity, trachea, bronchi, and esophagus. Only 5% of the patients had the distal involvement of the trachea, and the involvement of the lung parenchyma is very rare, which is seen in, 1% of all cases (5). Therefore, patients present most commonly with hoarseness followed by stridor, cough, and dyspnea. Risk factor for malignant conversion includes smoking, prior irradiation, HPV-6. A recent study showed the presence of E6 and E7 oncogenes and their transcripts in HPV-positive lung cancer cases that are prerequisite for cancer development, thus reinforcing further the hypothesis that HPV could be a co-factor in bronchial carcinogenesis (6).Our patient had history of smoking as the only risk factor for malignant conversion.

Progressively increased expression of p53 and pRb proteins along with a reduced expression of p21^WAF1 protein appears to be significant subsequent events in the progression to carcinoma (7). Talierco et al. (8) reported 100% of patients with adult onset RRP had concurrent HPV infection of the oral cavity; however, our patient had no evidence of oral cavity HPV infection on physical examination. Bronchoscopic pictures were suggestive of papillary lesion although association with HPV can’t be commented upon as patient refused for further testing. A literature review of RRP case reports revealed that patients usually have the diagnosis of RRP many years before evidence of malignant transformation (9-12). In contrast, our patient had evidence of malignant transformation about six months after diagnosis of respiratory papillomatosis.

DiMarco et al. (13) were the first to report the presence of the multiple RRP of the tracheobronchial tree with malignant degeneration, in 1978. One other case report showing coexistence of multiple squamous cell papilloma and carcinoma in the upper trachea with severe airway obstruction has been reported (14). A case study done in Taiwan suggests that HPV infection is an important risk factor for lung cancer among women (15).

Surgical excision of RRP is the current standard of care with objective of preserving adequate voice quality and airway patency (16). Lasers can also be employed for surgical excision of RRP. Either cutting/ablating lasers (CO2 and thallium lasers), or photoangiolytic lasers such as pulsatile (PDL) and potassium- titanil-phosphate lasers (KTP) can be used. Both KTP and PDL lasers are safe and effective for in office treatment of RRP (17). Microdebriders have distinct advantages over lasers and cold instruments because of their shorter operating time and absence of thermal injury (18). Adjuvant therapies for RRP include the usage of immunomodulators such as IFN, antivirals such as Cidofovir, Angiogenesis inhibitor (Bevacizumab) and PDL-1 inhibitor (19). The development of HPV- 1 vaccination is perhaps the most important modality in the management of RRP, by preventing infection with papilloma virus.

Conclusion

To the best of our knowledge, this is the first case report of coexisting respiratory papillomatosis with small cell carcinoma lung. Thus, coexistence of malignancy or malignant degeneration of respiratory papillomatosis is although unusual but can still occur without the associative factors. Patients with RRP should be radiographically monitored at regular intervals for pulmonary involvement and further evaluation actively pursued if any suspicion of malignancy arises.

References

1. Magid MS, Chen YT, Soslow RA, Boulad F, Kernan NA, Szabolcs P. Juvenile-onset recurrent respiratory papillomatosis involving the lung: A case report and review of the literature. Pediatr Dev Pathol. 1998 Mar-Apr;1(2):157-63. [CrossRef] [PubMed]
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3. Kashima HK, Shah F, Lyles A, Glackin R, Muhammad N, Turner L, Van Zandt S, Whitt S, Shah K. A comparison of risk factors in juvenile-onset and adult-onset recurrent respiratory papillomatosis. Laryngoscope. 1992 Jan;102(1):9-13. [CrossRef] [PubMed]
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Cite as: Sharma P, Kumar A, Janapati B, Jain AK. Respiratory papillomatosis with small cell carcinoma: case report and brief review. Southwest J Pulm Crit Care. 2020;21:141-6. doi: https://doi.org/10.13175/swjpcc064-20 PDF

December 2020 Pulmonary Case of the Month: Resurrection or Medical Last Rites?

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

An 88-year-old man who has been short of breath and febrile up to 101.5° F for the past day presented on October 20, 2020. He has no known sick contacts or exposure to COVID-19.

PMH, SH, and FH

• No reported pulmonary history although he had a Xopenex MDI which he rarely used.
• Coronary artery disease with prior coronary artery bypass grafting (1978); multiple subsequent stents; chronic atrial fibrillation; pacemaker (Micra)
• Stage 3-4 CKD (creatinine 1.95)
• Chronically on warfarin

Physical Examination

• Temp 37.3, Sat 92% on RA, 95% on 2 lpm,
• Lungs: Few crackles in right upper chest
• CV: regular, no murmur
• Ext: 1 to 2+ edema (chronic, uses TED hose)

Which of the following is/are the most likely diagnosis? (Click on the correct answer to be directed to the second of seven pages)

1. Community-acquired pneumonia
2. Congestive heart failure
3. COVID-19
4. 1 and 3
5. Any of the above

Cite as: Wesselius LJ. December 2020 Pulmonary Case of the Month: Resurrection or Medical Last Rites? Southwest J Pulm Crit Care. 2020;21(6):128-37. doi: https://doi.org/10.13175/swjpcc065-20 PDF