Background: Using analysis of air samples from the workplace, we report on one case of pneumoconiosis in an individual who has been working in a polytetrafluoroethylene (PTFE) spraying process for 28 years. Case presentation: The patient was diagnosed with granulomatous lung disease caused by PTFE using computed tomography (CT), lung biopsy and electron microscopy. To assess the qualitative and quantitative exposure to PTFE in workplace, Fourier transform infrared spectroscopy (FT-IR), energy-dispersive X-ray spectroscopy (EDX) and thermogravimetric analysis (TGA) were performed on air samples from the workplace. The presence of PTFE particles was confirmed, and the airborne concentration of PTFE was estimated to be 0.75 mg/m . Conclusions: This case demonstrates that long-term exposure to PTFE spraying can cause granulomatous lung lesions such as pneumoconiosis; such lesions appear to be caused not by the degradation products of PTFE from high temperatures but by spraying the particles of PTFE. Along with air-sampling analysis, we suggest monitoring the concentration of airborne PTFE particles related to chronic lung disease. Keywords: Occupational diseases, Pneumoconiosis, Polytetrafluoroethylene Background particle-induced chronic lung disease has not been re- Fluoropolymers are fluorinated carbon-based polymers ported. Furthermore, measurement of the airborne concen- with multiple carbon-fluorinated bonds . Fluoropoly- tration of PTFE particles has not been reported. mers have properties of lubricity, chemical inertness, Here, using analysis of air samples from a workplace, strength, plasticity, and thermal stability. These materials we report one case of small airway-centered granuloma- are widely used in gaskets, coating, self-lubricating bearings, tosis pneumonitis after long-term exposure to the PTFE food manufacturing machinery, household products such spray-coating process. An exposure assessment was also as nonstick cooking utensils, and other applications . performed. The present study protocol was reviewed Acute lung toxicity from PTFE fumes and chronic foreign and approved by the institutional review board of body reactions from injected PTFE have been reported. Keimyung University Dongsan Medical Center (IRB No. PTFE degrades at temperatures higher than 360 °C, pro- 2016–02–024-005). duces toxic fumes, and causes severe lung injury [3, 4]. Fluorocarbon-containing aerosol product exposure due to Case presentation spraying can also cause acute lung injury [5–7]. Chronic The case lung disease found in PTFE-spraying workers has been Patient reported . However, the pathophysiology of PTFE Male patient aged 46 years at the time of the first visit * Correspondence: email@example.com for diagnosis. Department of Occupational and Environmental Medicine, Keimyung University Dongsan Medical Center, 1095 Dalgubeol-daero, Dalseo-gu, Daegu 42601, South Korea Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Lee et al. Annals of Occupational and Environmental Medicine (2018) 30:37 Page 2 of 7 Chief complaint definitive diagnosis and to identify the cause of the Abnormal chest X-ray during health examination. pneumoconiosis. On histologic examination, the specimen revealed mainly small airway-centered granulomatous History of present illness micronodular lesions and multinucleated giant cells con- The patient displayed no symptoms while working in taining amorphous transparent particles (Fig. 2a and b). the PTFE spray-coating process for 28 years. Polarizing microscopic findings of the same multinucleated giant cells shown in Fig. 2b reveals the birefringent particle Social history (Fig. 2c). Transmission electron microscopic features high- The patient had never smoked or consumed alcohol. light the intracytoplasmic electron lucent amorphous materials (asterisks) in the histiocytes (Fig. 2d). Scanning Past medical history electron microscopic features and comparison element The patient had no history of hypertension, diabetes, or mapping of fluorine reveals the presence of fluorine ele- tuberculosis. ments in the pulmonary lesion. Scanning electron micro- scopic features of the lesion revealing fluorine elements Family history show multiple round to oval granular material measuring The family history was unremarkable and noncontributory. 2–6 μm(Fig. 2e and f). The energy-dispersive X-ray spec- troscopy (EDX) spectrum of a particle in a round particle Clinical process found a multinucleated giant cell showing a prominent The patient was diagnosed with pneumoconiosis by rou- peak for fluorine (F) but with other associated elements tine chest screening with plain films (Fig. 1a). He did such as carbon (C) and oxygen (O) (Fig. 2g and h). FT-IR not complain of cough, dyspnea, or other respiratory was performed for elemental analysis of the lung tissue. symptoms at the first visit to the hospital. On physical The analysis showed vibration on a similar wavelength to examination, the lung sounds were clear. Sputum cul- the results of standard PTFE and PTFE spray solution, tures and AFB stain tests were performed to exclude tu- which had been used in the factory. This showed the pres- berculosis; both were negative. Diagnostic computed ence of PTFE in the lung tissue (Fig. 3). tomography (CT) was performed and revealed numer- ous tiny scattered nodules and a few calcified nodules in Intervention and outcome both lungs. Multiple nodules showed peri-lymphatic dis- Six months after the first visit, the patient complained of tribution without enlarged lymph nodes (Fig. 1b). Wedge chest pain and dyspnea. Since that time, he has been resection of the lung and a biopsy were performed for a prescribed Singulair for symptomatic relief. He visited Fig. 1 a Chest radiograph showing multiple bilateral nodules in both lung fields. b CT scan of the chest showing numerous tiny nodules with perilymphatic distribution without lymph-node calcification Lee et al. Annals of Occupational and Environmental Medicine (2018) 30:37 Page 3 of 7 Fig. 2 Histologic features of a case of polytetrafluoroethylene (PTFE) exposure-induced pulmonary granulomatous lesions (a and b). a The specimen shows mainly small airway- centered granulomatous micronodular lesions (arrow). b Higher magnification of the specimen shows multinucleated giant cells containing amorphous transparent particles (black arrows). c Polarizing microscopic finding of the same multinucleated giant cell found in Fig. b reveals the birefringent particle (white arrows). a to c Hematoxylin-Eosin stain (Magnification: A: × 40, B and C: × 400). d Transmission electron microscopic feature show intracytoplasmic electron lucent amorphous materials (asterisks) in the histiocyte. e and f Scanning electron microscopic feature (e) and comparing element mapping of fluorine (yellow) reveals the presence of fluorine in the pulmonary lesion. g The scanning electron microscopic feature of the lesion revealing fluorine in Fig. f shows multiple round to oval granular material measuring 2–6 μm. (Original magnification, d:× 3500, e and f: × 500, g × 5000). h: Energy-dispersive X-ray spectroscopy (EDS) spectrum of a particle in a round particle (target 1 shown in Fig. g) found in multinucleated giant cell showing a prominent peak for fluorine (F) but with other associated elements such as carbon (C), and oxygen (O) the outpatient clinic every year and underwent follow-up sheet, the spray solution contains 55–65% PTFE. Subse- tests to follow the progress of the pneumoconiosis. He quently, the pans are transported to a heat oven, and a quit his job in September 2016. drying process is performed. The coating process includes bottom, middle and top coating. Bottom coating is per- Occupational history formed at 180 °C, while middle and top coating occurs at The work process at the workplace is summarized as fol- 400 °C. The dried pans are transported back through the lows. Round-shaped plates are processed into a frying-pan spraying process until they are coated twice. Finally, the shape by a press machine. Surface sanding is then per- three layer-coated pans are assembled with handles. formed to increase the absorption rate of paint and coat- The patient had been working for 28 years in only ing material on the surface. After surface sanding, spray the PTFE spraying process. Spraying was performed coating is performed. According to the material safety data 2000–3000 times a day, 50 cm away from the face. Lee et al. Annals of Occupational and Environmental Medicine (2018) 30:37 Page 4 of 7 To conduct quantitative analysis of the particles, air samples were again collected. Personal and regional sam- ples were gathered from the workplace. The personal sam- ple was taken from the patient’s breathing zone using a cyclone sampler with a glass-fiber filter with a 1 μmpore size. The flow rate was 1.5 L/min, and the sample was col- lected for 6 h. A sample of 2.048 mg was taken. The re- gional sample was taken from the top of the hood using the cyclone sampler, and a PVC filter with a 5 μmpore size was used. The flow rate was 1.5 L/min, and the sam- ple was taken for 6 h. A sample of 0.241 mg was taken. Thermogravimetric analysis (TGA) was then performed to differentiate the PTFE particles. A filter from the patient was divided into four, and TGA was performed. With the Fig. 3 FT-IR analysis of the lung tissue of the patient shows the patient’s sample, prominent weight loss was shown at presence of PTFE compared with the standard PTFE peak result 550–600 °C. In total, 0.40994 mg of the sample weight was reduced at 550–600 °C (Fig. 4a). The airborne The patient worked 10 h a day, 6 days a week, with- concentration of PTFE was estimated to be 0.75 mg/m . out a respirator. The heat oven process for drying the The regional sample showed no prominent weight loss at pans was conducted approximately 1 m away from 550–600 °C (Fig. 4b). To confirm that the weight loss the spraying process; the heat oven is a long, closed point of the personal sample corresponded with PTFE, structure with two small exits at opposite ends. three types of PTFE spray solutions were used to coat the pans in the workplace for the top, middle, and primary Work environment coatings and were analyzed by TGA. All three solu- Fluorocarbon polymers, such as PTFE, are not target tions showed prominent weight loss at 550–600 °C, chemicals for routine work environment monitoring in which corresponded with the results of the personal Korea, so to identify exposure to PTFE, work environ- sample analysis (Fig. 4c). ment air sampling was performed. First, qualitative ana- lysis of air samples was conducted to confirm the Conclusion presence of PTFE particles. Personal and regional sam- This is a case report of small airway-centered granulo- ples were gathered from the workplace. A sample was matosis caused by PTFE particles from the spraying taken from the breathing zone of the patient while work- process with a description of the air concentration of ing on the spraying process. A regional sample was PTFE in a workplace. The patient was diagnosed with taken from the top of the hood, approximately 2 m high, granulomatous lung disease from PTFE using CT and near the spraying process. Airborne sample collection lung pathology and electron microscopic findings, which was performed in accordance with the NIOSH Manual are compatible with a previously reported case . We of Analytical Methods . A cyclone and glass-fiber filter confirmed the presence of PTFE particles in the lung tis- was used to collect the air samples. The flow rate was sue by SEM and EDX of lung tissue. Additionally, the air 1.6 L/min. The samples were collected for 6 h. For qualita- sample from the workplace was analyzed by FT-IR, tive analysis of PTFE in the air samples, Fourier transform EDX, and TGA. The presence of PTFE was confirmed, infrared spectroscopy (FT-IR) spectrometry was per- and the diameter of the particles was measured. The air formed. The personal sample from the spray worker concentration was also calculated. − 1 shows strong vibration at 1148.6 and 1204.9 cm .FT-IR The patient’s CT findings showed numerous tiny scat- of a PTFE spray solution demonstrates peaks at 1117.7 tered nodules and a few calcified nodules in both lungs; − 1 and 1265.5 cm . The spectra of the individual samples however, these were distinguishable from those of classic were consistent with the C-F bond characteristics of the silicosis. The CT findings of typical silicosis include sprays used at the factory. Scanning electron microscopy upper-lobe-dominant peri-lymphatic distribution of mul- (SEM) analysis and EDX were then performed with the tiple 2–5 mm nodules with hilar and mediastinal lymph same samples to confirm the presence of PTFE particles node enlargement and calcification . Therefore, we and measure the size of the particles. Fine particles with a ruled out silicosis as a diagnosis in this patient. smooth, round surface showed fluorine and carbon peaks The respiratory effects of PTFE are usually focused on on the EDX spectrum. The particles found in the personal acute toxicity. Heated PTFE particles may cause symp- samples measured 1–22 μm by SEM; particles smaller toms that range from mild flu-like symptoms to severe than 1 μm were also found. symptoms, such as pulmonary edema [11, 12]. Various Lee et al. Annals of Occupational and Environmental Medicine (2018) 30:37 Page 5 of 7 Fig. 4 a Thermogravimetric analysis of the patient’s personal air sample shows prominent weight loss at 550–660 °C. A total of 0.40994 mg of the sample weight was reduced at 550–600 °C. b Thermogravimetric analysis of the regional sample shows weight loss near 450 °C, and no prominent weight loss was found at 550–600 °C. c Thermogravimetric analysis of the PTFE spray solution shows prominent weight loss at 550–600 °C previous studies have suggested that ultrafine particles vocal cord injection for treating paralyzed vocal cords from the heating of PTFE severely injure the lungs, and , suburethral injection for the treatment of vesicour- the particles lose their toxicity after becoming coagu- eteral reflux in children , acetabular cup for hip re- lated into larger homogeneous particles [4, 13]. Acute placement , and as a bulking agent for the treatment pulmonary toxicity due to fluorocarbon-containing aero- of stress urinary incontinence  has been reported. sol spray has been reported  from various work pro- Foreign-body giant cell reaction and a glassy-appearing cesses, such as those of waterproof leather, fabric spray, material in multinucleated giant cells are typical patho- floor-stain protector, rust-proofing spray, grout sealer, logical findings of Teflon-induced foreign-body reaction and ski wax [15–18]. Choi et al. reported for the first . Like these cases, multinucleated giant cells contain- time chronic pulmonary granulomatosis associated with ing glassy-appearing material were frequently noted in exposure to PTFE . The spraying process and the present case. aerosolized PTFE were excluded as the cause of small This patient worked on the same process for 28 years airway-centered granulomatosis because of the stability and never worked on other processes, including the of PTFE in a liquid formulation . However, nonde- heat-drying process. In our study, we collected both per- graded PTFE can induce an immunologic reaction in sonal and regional samples from the workplace and ana- body tissue. PTFE has been used in various medical pro- lyzed them to identify the cause of small airway-centered cesses because it is well tolerated by the body tissue, not granulomatosis. We confirmed the presence of PTFE parti- resorbed, and disperses in various fluids. However, cles of up to 20 μmbyFT-IR,EDX,and TGAfromthe per- foreign-body granulomatous reactions after the injection sonal air samples. FT-IR, SEM and EDX analysis of the of PTFE have been reported, including Teflon granu- patient’s lung tissue showed the presence of 2–6 μmPTFE loma formation after microvascular decompression , particles. The size of the pyrolyzed PTFE particles was Lee et al. Annals of Occupational and Environmental Medicine (2018) 30:37 Page 6 of 7 0.02–0.2 μmat560 °C and0.02–0.07 μm at 370 °C. Al- Authors’ contributions SY and IC were responsible for the concept and design of the study. IH and ML though pyrolyzed PTFE can aggregate into larger particle performed air sampling and analysis of the working environment. SP performed size, only particles pyrolyzed from high temperature up to FTIR and electron microscopy and EDX analysis. HJ conducted an analysis of 560 °C aggregated into large globular agglomerates, while pathology. WC reviewed the patient’s clinical examination and overall clinical findings. NL and KB participated in the overall study and synthesized the findings particles pyrolyzed from 370 °C aggregated into chain to describe the script. All authors read and approved the final manuscript. shapes up to 1.6 μminsize. In our study, the PTFE particles from air sampling measured 1–22 μmbyelectron Ethics approval and consent to participate This study was approved by Keimyung university Dongsan medical center microscopy, and the size corresponded to reported PTFE institutional review board. The number of approval is 2016–02–024-008. powder size (7.6 ± 8.5 μm) . The particle size identified in the lungs was 2–6 μm. The coating process occurred at Competing interests The authors declare that they have no competing interests. 180–400 °C; the size of pyrolyzed particles formed at this temperature would be smaller. Additionally, aggregated Publisher’sNote pyrolytic products of PTFE showed variety in shape such as Springer Nature remains neutral with regard to jurisdictional claims in spherical, undulating, concave, bowl or doughnut-shaped published maps and institutional affiliations. with a thickened peripheral portion . In this study, the Author details samples of PTFE collected from workplace revealed a Department of Occupational and Environmental Medicine, Keimyung round regular shape. Therefore, the particles are more likely University Dongsan Medical Center, 1095 Dalgubeol-daero, Dalseo-gu, Daegu to have originated from the spray process. As a result, we 42601, South Korea. Nano Convergence Practical Application Center, Daegu, South Korea. Korean Industrial Health Association, Daegu, South Korea. suggestthatthe smallairway-centered granulomatosis diag- Department of Preventive Medicine, Keimyung University School of nosed in this patient was caused by the aerosolized PTFE 5 Medicine, Daegu, South Korea. Department of Internal Medicine, Keimyung particles from the spraying process. University School of Medicine, Daegu, South Korea. Department of Pathology, Keimyung University School of Medicine, Daegu, South Korea. Patient lesions seemed to be caused by prolonged ex- posure to the aerosolized PTFE particles from the spray- Received: 24 January 2018 Accepted: 27 May 2018 ing process, without acute respiratory symptoms. One limitation of this study is that TGA was not performed References on the collected lung tissue. Furthermore, the health ef- 1. Hays HL, Spiller H. Fluoropolymer-associated illness. Clin Toxicol (Phila). fects of particles formed by pyrolysis cannot be excluded. 2014;52(8):848–55. 2. Teng H. 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Published: Jun 4, 2018