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.

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.

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.

Phenotypes and Characterization of COPD: A PULMONARY REHABILITATION PERSPECTIVE.

Phenotyping and the characterization of chronic obstructive pulmonary disease (COPD) is currently an active area of interest. The perspectives gleaned from evaluating COPD in the context of exercise lend new insights into this endeavor. Pulmonary rehabilitation centers are uniquely positioned to generate such clinical observations and have enhanced an understanding of the disease processes that are involved in COPD. This review and commentary discusses the various patterns of exercise intolerance and characterizes COPD from the perspectives of clinicians caring for persons with COPD.

Libby Amphibole Disease: Pulmonary Function and CT Abnormalities in Vermiculite Miners.

OBJECTIVE: This article describes radiologic and pulmonary function findings among miners exposed to Libby amphibole. Computed tomography (CT) permits the detection of the characteristic thin, lamellar pleural thickening (LPT). METHODS: Individuals who worked at the mine for a minimum of 6 months had chest CT and pulmonary function tests. RESULTS: Pleural thickening was noted in 223 (87%) of the 256 miners, parenchymal abnormalities in 49 (19%). LPT, found in 151 (68%), was associated with low values of forced vital capacity and diffusion capacity and significantly lower values in all pulmonary function tests when associated with parenchymal abnormalities. CONCLUSION: Eighty-seven percent of miners exposed to Libby Amphibole had pleural abnormalities on CT. LPT alone, and more so with parenchymal abnormalities, resulted in decreased pulmonary function. The importance of this easily missed LPT is demonstrated by its high frequency and significant functional effects.

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.

3D nano- and micro-patterning of biomaterials for controlled drug delivery.

Recently, there has been an emerging interest in controlling 3D structures and designing novel 3D shapes for drug carriers at nano- and micro-scales. Certain 3D shapes and structures of drug particles enable transportation of the drugs to desired areas of the body, allow drugs to target specific cells and tissues, and influence release kinetics. Advanced nano- and micro-manufacturing methods including 3D printing, photolithography-based processes, microfluidics and DNA origami have been developed to generate defined 3D shapes and structures for drug carriers. This paper reviews the importance of 3D structures and shapes on controlled drug delivery, and the current state-of-the-art technologies that allow the creation of novel 3D drug carriers at nano- and micro-scales.

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.