Recognizing the pleura in asbestos-related pleuropulmonary disease: Known and new manifestations of pleural fibrosis.

Pleural thickening (PT) is a major consequence of exposure to all fiber types of asbestos. In recent decades, it is more prevalent than parenchymal asbestosis. Its manifestations occupy a full clinical and radiographic spectrum. Six major manifestations can be identified: (a) acute pleuritis generally with effusion; (b) diffuse PT or fibrous pleuritis; (c) rounded atelectasis; (d) circumscribed PT or plaques; (e) chronic pleuritic pain; and (f) mesothelioma. Review of the experience of workers and community members in Libby, MT to asbestiform fibers in vermiculite has confirmed the appearance of these previously known benign and malignant asbestos-related diseases as well as a unique pleuropulmonary disease characterized as lamellar PT and associated with progressive decline in pulmonary function and pleuritic pain. Despite previous literature asserting that PT represents a marker for asbestos exposure without significant effect on pulmonary function and physiology, the experience of Libby amphibole (LA) disease, along with other studies, indicates that PT plays a role in declining vital capacity in those with prolonged or unusual exposures such as those arising from LA.

Case-fatality study of workers and residents with radiographic asbestos disease in Libby, Montana.

BACKGROUND: Vermiculite ore from Libby, Montana contains on average 24% of a mixture of toxic and carcinogenic amphibole asbestiform fibers. These comprise primarily winchite (84%), with smaller quantities of richterite (11%) and tremolite (6%), which are together referred to as Libby amphibole (LA). METHODS: A total of 1883 individuals who were occupationally and/or environmentally exposed to LA and were diagnosed with asbestos-related pleuropulmonary disease (ARPPD) following participation in communitywide screening programs supported by the Agency for Toxic Substances and Disease Registry (ATSDR) and followed up at the Center for Asbestos Related Disease (CARD) between 2000 and 2010. There were 203 deaths of patients with sufficient records and radiographs. Best clinical and radiologic evidence was used to determine the cause of death, which was compared with death certificates. RESULTS: Asbestos-related mortality was 55% (n = 112) in this series of 203 patients. Of the 203 deaths, 34 (17%) were from asbestos-related malignancy, 75 (37%) were from parenchymal asbestosis, often with pleural fibrosis, and 3 (1.5%) were from respiratory failure secondary to pleural thickening. CONCLUSIONS: Asbestos is the leading cause of mortality following both occupational and nonoccupational exposure to LA in those with asbestos-related disease.

Biodegradable Piezoelectric Force Sensor.

Measuring vital physiological pressures is important for monitoring health status, preventing the buildup of dangerous internal forces in impaired organs, and enabling novel approaches of using mechanical stimulation for tissue regeneration. Pressure sensors are often required to be implanted and directly integrated with native soft biological systems. Therefore, the devices should be flexible and at the same time biodegradable to avoid invasive removal surgery that can damage directly interfaced tissues. Despite recent achievements in degradable electronic devices, there is still a tremendous need to develop a force sensor which only relies on safe medical materials and requires no complex fabrication process to provide accurate information on important biophysiological forces. Here, we present a strategy for material processing, electromechanical analysis, device fabrication, and assessment of a piezoelectric Poly-l-lactide (PLLA) polymer to create a biodegradable, biocompatible piezoelectric force sensor, which only employs medical materials used commonly in Food and Drug Administration-approved implants, for the monitoring of biological forces. We show the sensor can precisely measure pressures in a wide range of 0-18 kPa and sustain a reliable performance for a period of 4 d in an aqueous environment. We also demonstrate this PLLA piezoelectric sensor can be implanted inside the abdominal cavity of a mouse to monitor the pressure of diaphragmatic contraction. This piezoelectric sensor offers an appealing alternative to present biodegradable electronic devices for the monitoring of intraorgan pressures. The sensor can be integrated with tissues and organs, forming self-sensing bionic systems to enable many exciting applications in regenerative medicine, drug delivery, and medical devices.

Lung cancer screening in patients with Libby amphibole disease: High yield despite predominantly environmental and household exposure.

BACKGROUND: Lung cancer screening with low-dose computed tomography (CT) scanning (LDCT) is accepted as a screening tool, but its application to populations exposed to recognized occupational or environmental carcinogens is limited. We apply LDCT to a population with a predominantly nonoccupational exposure to a recognized human lung carcinogen, Libby amphibole asbestos (LA). METHODS: Patients in an asbestos disease clinic in Libby, Montana who were aged 50 to 84 years, greater than or equal to 20 pack-year history of tobacco use (irrespective of quit date), and asbestos-related pleuropulmonary disease on high-resolution CT scan were offered free annual lung cancer screening over a 39-month period. RESULTS: Of 2897 clinic patients, 1149 (39.7%) met eligibility criteria, and 567 (49%) were screened with 1014 low-dose CT scans. Most screened patients had principally environmental (333 or 59%) or household exposure (145 or 25%) to LA. Seventeen primary lung cancers were identified, mostly in early stages: 10 at stage 1, two at stage 2, three at stages 3 to 4, and two at limited small-cell cancers. The screening yield was 1.9 at baseline scan and 1.5% on the first annual scan. CONCLUSIONS: Consistent with the guidelines of the National Comprehensive Cancer Network and American Association of Thoracic Surgery, LDCT for early lung cancer detection should be offered to people with significant exposure to occupational or environmental human lung carcinogens.

Yield of Low-Dose Computerized Tomography Screening for Lung Cancer in High-Risk Workers: The Case of 7189 US Nuclear Weapons Workers.

OBJECTIVES: To determine the lung cancer screening yield and stages in a union-sponsored low-dose computerized tomography scan program for nuclear weapons workers with diverse ages, smoking histories, and occupations. METHODS: We implemented a low-dose computerized tomography program among 7189 nuclear weapons workers in 9 nonmetropolitan US communities during 2000 to 2013. Eligibility criteria included age, smoking, occupation, radiographic asbestos-related fibrosis, and a positive beryllium lymphocyte proliferation test. RESULTS: The proportion with screen-detected lung cancer among smokers aged 50 years or older was 0.83% at baseline and 0.51% on annual scan. Of 80 lung cancers, 59% (n = 47) were stage I, and 10% (n = 8) were stage II. Screening yields of study subpopulations who met the National Lung Screening Trial or the National Comprehensive Cancer Network Group 2 eligibility criteria were similar to those found in the National Lung Screening Trial. CONCLUSIONS: Computerized tomography screening for lung cancer among high-risk workers leads to a favorable yield of early-stage lung cancers. Public Health Implications. Health equity and efficiency dictate that screening high-risk workers for lung cancer should be an important public health priority.

Pulmonary infarction secondary to pulmonary embolism: An evolving paradigm.

BACKGROUND AND OBJECTIVE: Pulmonary infarction (PI) from pulmonary embolism (PE) remains an entity of unclear aetiology. PI has been thought to occur in elderly patients with cardiopulmonary disease. We hypothesize younger patients without cardiopulmonary comorbidities are at highest risk. Our study aims to characterize PI clinically and radiographically, determine associated risk factors and determine their clinical significance. METHODS: We conducted a single-centre retrospective review of 367 consecutive patients with PE. Clinical and radiographic data were compared between patients with and without PI using chi-square and F-tests. Univariate and multivariate analyses were performed to evaluate risk factors for PI. RESULTS: PI occurred in 62 of 367 patients with acute PE (16.9%). Patients with PI were significantly younger (48 ± 20.3 vs 59.6 ± 17.2 years, P < 0.01), with lower pulmonary embolism severity index (PESI) scores (73.7 ± 38.1 vs 91.9 ± 37.5 years, P < 0.01) and endorsed chest pain with significantly higher frequency (65% vs 39%, P < 0.01). There was no significant difference in other clinical symptoms, hospital length of stay or mortality between groups. Presence of radiographic cardiopulmonary disease was significantly lower in patients with PI (emphysema: 5% vs 22%, P = <0.01; aortic atherosclerosis: 23% vs 43%, P = <0.01). In multivariate analysis, age ≤33 (OR 3.5 CI: 1.37-8.95, P < 0.01), chest pain (OR 2.15 CI: 1.15-4.00, P = 0.02) and pleural effusion (OR 2.18 CI: 1.08-4.41, P = 0.03) increased PI risk and presence of emphysema decreased risk (OR 0.21 CI: 0.06-0.70, P = 0.01). CONCLUSION: Younger patients without cardiopulmonary comorbidities are at highest risk of PI. Chest pain and pleural effusion significantly increased risk of PI while presence of radiographic emphysema reduced risk.

Association Between CD4+, Viral Load, and Pulmonary Function in HIV.

PURPOSE: The antiretroviral therapy era has shifted the epidemiology of HIV-associated diseases, increasing the recognition of non-infectious pulmonary complications secondary to HIV. We aimed to determine the association between CD4+, viral load, and pulmonary function in individuals with uncontrolled HIV, and determine how changes in these parameters are associated with pulmonary function longitudinally. METHODS: This is a retrospective observational study of individuals with HIV who underwent pulmonary function testing in an urban medical center between August 1997 and November 2015. RESULTS: Of the 146 participants (mean age 52 ± 10 years), 49% were Hispanic, 56% were men, and 44% were current smokers. CD4+ <200 cells/µl was associated with significant diffusion impairment compared to CD4+ ≥200 cells/µl (DLCO 56 vs. 70%, p = <0.01). VL (viral load) ≥75 copies/ml was associated with significant diffusion impairment compared to VL <75 copies/ml (DLCO 60 vs. 71%, p = <0.01). No difference in FEV1, FEV1/FVC, or TLC was noted between groups. In univariate analysis, CD4+ and VL correlated with DLCO (r = +0.33; p = <0.01; r = -0.26; p = <0.01) and no correlation was noted with FEV1, FEV1/FVC, or TLC. Current smoking and history of AIDS correlated with DLCO (r = -0.20; p = 0.03; r = -0.20; p = 0.04). After adjusting for smoking and other confounders, VL ≥75 copies/ml correlated with a 11.2 (CI 95% [3.03-19.4], p = <0.01) decrease in DLCO. In Spearman's Rank correlation, there was a negative correlation between change in VL and change in DLCO over time (ρ = -0.47; p = <0.01). CONCLUSION: The presence of viremia in individuals with HIV is independently associated with impaired DLCO. Suppression of VL may allow for recovery in diffusing capacity over time, though the degree to which this occurs requires further investigation.

Pulmonary abnormalities as a result of exposure to Libby amphibole during childhood and adolescence-The Pre-Adult Latency Study (PALS).

BACKGROUND: The purpose of Pre-Adult Latency Study was to evaluate lung findings among adults who had been environmentally exposed to Libby Amphibole only during childhood and adolescence. METHODS: Recruitment was restricted to volunteers who attended primary and/or secondary school, lived in Libby, MT, prior to age 23 years for males and 21 years for females and subsequently left the area. Subjects completed exposure and respiratory questionnaires, underwent pulmonary function tests (PFTs), and chest CT scans. A Pleural Score was calculated for degree and extent of pleural thickening. Logistic regression and multivariate linear regression were used. RESULTS: Of the 219 who met inclusion criteria, 198 participated. Pleural thickening was found in 96 (48%) of 198 participants. In almost half of these, it was of the lamellar type, not generally seen in exposure to other asbestos. Environmental Libby amphibole exposure was associated with pleural thickening, and the likelihood of pleural thickening increased with the number of years lived in the area. An inverse association between Pleural Score and PFT was found, which remained significant for FVC and DLco after additional sensitivity analyses. CONCLUSIONS: Cumulative environmental exposure was associated with risk of pleural thickening. Among this cohort, quantitative measures of pleural thickening were associated with decreased PFT. Am. J. Ind. Med. 60:20-34, 2017. © 2016 Wiley Periodicals, Inc.

Asbestos, asbestosis, smoking, and lung cancer. New findings from the North American insulator cohort.

RATIONALE: Asbestos, smoking, and asbestosis increase lung cancer risk in incompletely elucidated ways. Smoking cessation among asbestos-exposed cohorts has been little studied. OBJECTIVES: To measure the contributions of asbestos exposure, asbestosis, smoking, and their interactions to lung cancer risk in an asbestos-exposed cohort and to describe their reduction in lung cancer risk when they stop smoking. METHODS: We examined lung cancer mortality obtained through the National Death Index for 1981 to 2008 for 2,377 male North American insulators for whom chest X-ray, spirometric, occupational, and smoking data were collected in 1981 to 1983 and for 54,243 non-asbestos-exposed blue collar male workers from Cancer Prevention Study II for whom occupational and smoking data were collected in 1982. MEASUREMENTS AND MAIN RESULTS: Lung cancer caused 339 (19%) insulator deaths. Lung cancer mortality was increased by asbestos exposure alone among nonsmokers (rate ratio = 3.6 [95% confidence interval (CI), 1.7-7.6]), by asbestosis among nonsmokers (rate ratio = 7.40 [95% CI, 4.0-13.7]), and by smoking without asbestos exposure (rate ratio = 10.3 [95% CI, 8.8-12.2]). The joint effect of smoking and asbestos alone was additive (rate ratio = 14.4 [95% CI, 10.7-19.4]) and with asbestosis, supra-additive (rate ratio = 36.8 [95% CI, 30.1-45.0]). Insulator lung cancer mortality halved within 10 years of smoking cessation and converged with that of never-smokers 30 years after smoking cessation. CONCLUSIONS: Asbestos increases lung cancer mortality among nonsmokers. Asbestosis further increases the lung cancer risk and, considered jointly with smoking, has a supra-additive effect. Insulators benefit greatly by quitting smoking.

Diffusing capacity and forced vital capacity in 5,003 asbestos-exposed workers: relationships to interstitial fibrosis (ILO profusion score) and pleural thickening.

BACKGROUND: Asbestosis is an interstitial lung disease whose radiographic severity has long been graded by the International Labour Office (ILO) profusion score. Its effect on pulmonary function is further impacted by asbestos related pleural thickening. OBJECTIVES: This report aims to describe the relationships between radiographic grading of interstitial and pleural fibrosis and a key test of pulmonary function, the diffusing capacity, which measures gas exchange and has rarely been assessed in large groups, and to confirm the relationship to an independent test of pulmonary function, the vital capacity, which measures a mechanical property of the lungs. METHODS: The data were derived from a survey during the period 1997-2004 of 5,003 workers (all white males) exposed to asbestos in various trades. Tests included chest radiographs read by a certified expert ("B") reader, forced vital capacity (FVC), and carbon monoxide diffusing capacity (DLco). Cigarette smoking was adjusted for in the predictive equation for DLCO . Workers were evaluated at a mobile facility at work sites in four southern states. RESULTS: Both diffusing capacity and vital capacity were negatively correlated with profusion score over the full spectrum of radiographic severity. ILO profusion scores 0/1 (conventionally classified as normal) and 1/0 (conventionally classified as abnormal) were associated with similar diffusing capacity and vital capacity values. The highest profusion scores were associated with a greater proportionate decrease in diffusing capacity than in FVC. Both tests showed an effect of pleural fibrosis. CONCLUSIONS: Both radiographic severity graded by the profusion score and pleural thickening are correlated with two independent measures of pulmonary function. FVC (which had been reported in smaller work forces) and DLCO (which has not been reported). Both measures show a decrease from normal to intermediate (0/1, 1/0) scores and a further decrease with greater scores, demonstrating the consistency of radiographic and functional assessments.

Lung cancer associated with cystic airspaces.

OBJECTIVE: The objectives of this study were to determine the frequency of lung cancers associated with a discrete cystic airspace and to characterize the morphologic and pathologic features of the cancer and the cystic airspace. MATERIALS AND METHODS: We reviewed all diagnosed cases of lung cancer resulting from baseline screening (n=595) and annual screening (n=111) in the International Early Lung Cancer Action Program to identify those abutting or in the wall of a cystic airspace. We also reviewed the pathologic specimens. RESULTS: A total of 26 lung cancers were identified abutting or in the wall of a cystic airspace. Of these, 13 were identified at baseline (13/595, 2%) and 13 at annual screening (13/111, 12%), which was significant (p<0.0001). The median circumferential portion of wall involved was less for the annual cancers than for the baseline ones, but this difference did not reach significance (90° vs 240°, p=0.07). The diagnosis was adenocarcinoma in all but three cases. Histologic analysis showed that the cystic space was a bulla, a fibrous walled cyst without a defined lining, or a pleural bleb and that in all but one case, the tumor was eccentric relative to the airspace and the wall of the airspace was unevenly thickened. CONCLUSION: At annual repeat CT screening, the finding of an isolated cystic airspace with increased wall thickness should raise the suspicion of lung cancer.

PFT interpretive strategies: American Thoracic Society/ European Respiratory Society 2005 guideline gaps.

All pulmonologists, including those recently completing training, should be competent in critically evaluating and interpreting pulmonary function tests (PFTs). In addition, some authorities recommend that respiratory therapists learn to provide preliminary PFT interpretations for the medical directors of PFT labs. The 2005 American Thoracic Society/European Respiratory Society guidelines for interpreting PFTs lack recommendations for the best reference equations for lung volumes and diffusing capacity of the lung for carbon monoxide (D(LCO)), and lack reference equations for non-whites. The pre-test probability of lung disease should be determined using a short questionnaire. The "nonspecific pattern" occurs in about 15% of patients referred to a PFT lab, but it has many clinical correlates and the course is usually benign. Less common PFT patterns and those resulting from comorbid conditions (such as obesity, respiratory muscle weakness, or heart failure) are not discussed by the guidelines. More than half of patients with interstitial lung disease have a normal ratio of D(LCO)/V(A) (alveolar volume), and many have a normal total lung capacity.

The evolving spectrum of pulmonary disease in responders to the World Trade Center tragedy.

On September 11, 2001, events at the World Trade Center (WTC) exposed residents ofNew York City to WTC dust and products of combustion and pyrolysis. The majority ofWTC-exposed fire department rescue workers experienced a substantial decline in airflowover the first 12 months post-9/11, in addition to the normal age-related declinethat affected all responders, followed by a persistent plateau in pulmonary function inthe 6 years thereafter. The spectrum of the resulting pulmonary diseases consists ofchronic inflammation, characterized by airflow obstruction, and expressing itself indifferent ways in large and small airways. These conditions include irritant-inducedasthma, non-specific chronic bronchitis, aggravated pre-existing obstructive lung disease(asthma or COPD), and bronchiolitis. Conditions concomitant with airwaysobstruction, particularly chronic rhinosinusitis and upper airway disease, and gastroesophagealreflux, have been prominent in this population. Less common have beenreports of sarcoidosis or interstitial pulmonary fibrosis. Pulmonary fibrosis and bronchiolitisare generally characterized by long latency, relatively slow progression, and asilent period with respect to pulmonary function during its evolution. For these reasons,the incidence of these outcomes may be underestimated and may increase overtime. The spectrum of chronic obstructive airways disease is broad in this populationand may importantly include involvement at the bronchiolar level, manifested as smallairways disease. Protocols that go beyond conventional screening pulmonary functiontesting and imaging may be necessary to identify these diseases in order to understandthe underlying pathologic processes so that treatment can be most effective.

A randomized trial comparing hypofractionated and conventionally fractionated three-dimensional external-beam radiotherapy for localized prostate adenocarcinoma : a report on acute toxicity.

PURPOSE: To compare acute gastrointestinal (GI) and genitourinary (GU) toxicity between patient groups with localized prostate adenocarcinoma, treated with conventionally fractionated (CFRT) and hypofractionated (HFRT) three-dimensional conformal external-beam radiotherapy (3D-CRT). PATIENTS AND METHODS: 91 patients were enrolled into a randomized study with a minimum follow-up of 3 months. 44 men in the CFRT arm were irradiated with 74 Gy in 37 fractions at 2 Gy per fraction for 7.5 weeks. 47 men in the HFRT arm were treated with 57 Gy in 17 fractions for 3.5 weeks, given as 13 fractions of 3 Gy plus four fractions of 4.5 Gy. The clinical target volume (CTV) included the prostate and the base of seminal vesicles. The CTV-to-PTV (planning target volume) margin was 8-10 mm. Study patients had portal imaging and/or simulation performed on the first fractions and repeated at least weekly. RESULTS: No acute grade 3 or 4 toxicities were observed. The grade 2 GU acute toxicity proportion was significantly lower in the HFRT arm: 19.1% versus 47.7% (chi(2)-test, p = 0.003). The grade 2 GU acute toxicity-free survival was significantly better in the HFRT arm (log-rank test, p = 0.008). The median duration of overall GI acute toxicity was shorter with HFRT: 3 compared to 6 weeks with CFRT (median test, p = 0.017). CONCLUSION: In this first evaluation, the HFRT schedule is feasible and induces acceptable or even lower acute toxicity compared with the toxicities in the CFRT schedule. Extended follow-up is needed to justify this fractionation schedule's safety in the long term.