Rounded Atelectasis After Exposure to Refectory Ceramic Fibres - A Case Report

Background: Refractory Ceramic bres (RCF) are man-made mineral bres used in high performance thermal insulation applications and mostly to line furnaces, kilns and other industrial heaters. Analogous to asbestos bres, RCF are respirable, show a pleural drift and can persist in human lung tissue for more than 20 years after exposure. Pleural changes such as localised or diffuse pleural thickening as well as pleural calcication were reported. Case presentation: A 45 years old man worked in high performance thermal insulation applications using refractory ceramic bres (RCF) for almost 20 years. During a biennial occupational medical prophylaxis to ensure early diagnosis of disorders caused by inhalation of aluminium silicate bres with X-ray including high-resolution computed tomography (HRCT) showed bilateral pleural thickening and a pleural calcication next to a rounded atelectasis. Asbestos exposure could be excluded. In pulmonary function test a restrictive lung pattern could be revealed. In work samples scanning electron microscopy (SEM) including energy dispersive X-ray analysis (EDX) classied aluminium silicate bres. X-ray powder diffraction and transmission electron microscopy (TEM) showed crystalline as well as amorphous bres. Conclusions: A comprehensive lung function analysis and in case of restrictive lung disorders additional CT scans are needed in RCF exposed workers in accordance to the guidelines for medical occupational examinations comparable to asbestos exposed workers.

and silicon oxide (SiO 2 ) in approximately proportion or in combination with minor amounts of other inorganic oxides (1). Therefore the RCF were named also as aluminium silicate bres. RCF were produced from melting and blowing or spinning process. As manufactured, RCF are in the form of bulk bres (1). The diameter of the bres depends on process parameters. Respirable bres with the greatest toxicological potential are WHO bres with a length > 5 µm, a diameter ≤ 3 µm and the length to diameter ratio of at least 3:1. These bres impede clearance by alveolar macrophages (1). Lockey et al. (2) showed that RCF can persist in human lung tissue for more than 20 years after exposure.
Analogous to asbestos bres, RCF showed a pleural drift. Pleural changes such as localised or diffuse pleural thickening as well as pleural calci cation were reported by LeMaster (3). Rounded atelectasis after asbestos exposure were described previously (4). In our opinion this is the rst report of rounded atelectasis in connection with calci ed pleural plaques following long-term RCF exposure.
Case Report Occupational history In 2000 a 45 year old Caucasian male worker (never smoker) started to work in a RCF processing plant.
For the rst three years he was employed at a suction station for processing vacuum mouldings by transferring RCF manually from packages into the suction station. He also operated a dry kiln for these vacuum mouldings. After drying the vacuum moulds they had to be cut or sawed to length manually, polished, and holes had to be drilled to attach heating units. The heating units were glued and clenched to the moulds. Finally two half-round moulds were assembled to form one round heating furnace. While working at the suction station and especially at the dry kiln, dust concentrations of RCF were measured.
Since 2004 he was assigned to the cartridge production line also working at the works bench with a lower exposure to RCF. Personalised measurements were taken at different production sectors within the plant in 2012, 2015, 2017 and 2018 as shown in Table 1. The worker performs endurance sport as running and soccer playing on a regular base. No pulmonary disease has been described before. No complaints were reported while being exposed to fumes, gases, dust or being in wet and cold weather. Breath sounds were reduced in the lower left side and the percussion note was dull. Lung expansion was decreased on the left side. Crackles could not be detected.

Radiological ndings
In chest X-rays (p.a. and lateral) showed localised pleural thickening with adhered costodiaphragmatic sinus on the left side and consecutively reduced volume of the left hemi thorax ( Figure 1).
Computer tomography scans presented bilateral pleural thickening especially paravertebral, with embedded pleural calci cation. Besides this a beginning rounded atelectasis with a "comet tail" sign is visible adherent to the pleura in the left. A volume reduction of the left lower lobe ( Figure 2) is seen.

Analysis of the insulating material
Techniques used for the material characterisation RC Fibre samples (aluminium silicate bres) called F3, F17 and F14 obtained from the processing plant as raw material RCF (indicated a) and RCF vacuum moulds (indicated b) were analysed. Scanning electron microscopy (SEM; Hitachi S-2300; Hitachi, Ltd., Tokyo, Japan) was used to identify bre geometry in addition to the microstructure of the bres. Energy dispersive X-ray spectroscopy (EDX) was used to determine the elementary composition. To increase the conductivity, all samples were sputtered with a ne layer of Au.
X-ray powder diffraction is a common technique to determine the crystal structure of materials. It was used to analyse the crystallinity of the RCF. X-ray powder diffraction in re ection mode was performed with an X'Pert Pro from PANalytical (CuKα radiation (λ = 1.5418 Å), 40 kV, 40 mA). The measurements occurred between 10° and 80° with a step size of 0.033°. With this technique, monochromatic X-ray radiation, generated by a cathode ray tube, creates constructive interference with the sample when the conditions ful l Bragg's law: Here n is an integer, λ is the wavelength of the monochromatic X-ray radiation (most common: CuKα radiation λ = 1.5418 Å), d is the distance between two lattice planes and θ (Theta) is the diffraction angle.
The intensity of the diffracted beam is detected in dependence of the angle 2θ, measured in degree (deg), between the incident beam and the detector. The resulting diffraction "peaks" (re ections) can be converted into d-spacings, which allows the identi cation of the material since these d-spacings are unique for each compound. While crystalline substances produce a pattern of sharp re ections with different intensities, amorphous compounds only produces a broad background signal. Further information about this technique can be found, for example, in the review article of Bunaciu et al. (12).
The crystallinity of the RC bres was additionally investigated with transmission electron microscopy (TEM) and electron diffraction. The TEM images were recorded with a Philips CM30/STEM (300 kV, LaB 6 cathode) equipped with a GATAN digital camera.
In gure 6 the results of the X-ray powder diffraction of the samples F3 and F17 were presented. The raw material (indicated a) as well as the RCF vacuum moulds (indicated b) showed no re ections, only a broad background signal, which indicates the amorphous character of these samples. The electron diffraction con rms these results; no re ections were visible as well.
In contrast, the bres of the samples F14 are crystalline. The X-ray powder diffraction (Fig. 7) of the sample F14a and F14b shows sharp re ections for speci c angles, which indicates the crystallinity of this sample. The bres were identi ed with a crystallographic data base by the diffraction pattern as The electron diffraction con rms these results. Figure 9 shows  (14) at the saw position 1 and 3, at the dry kiln, at the work bench and the cartridge production. Amorphous and crystalline RCF were detectable during suction processing, drying and in all manual working steps during cartridge production. The bres did not change physical properties during different processing steps. As shown in Figure 5 bres had various lengths with a high proportion of long bres meeting the WHO criteria as respirable bres.
During a routine medical examination a restrictive lung function analysis was obvious. In X-ray including chest CT scans diffuse pleural thickening, calci cations and a rounded atelectasis could be con rmed.
The patient and safety engineer excluded any asbestos exposure at the workplace. The changes were ascribed to RCF exposure at the workplace.

Animal studies
Animal data indicated there is a risk of pleural changes and malignancies after RCF exposure. Hesterberg and Mast showed in 1995 that exposure to RCF induced lung brosis, lung tumours and mesotheliomas in rats and hamsters (15,16). RCF exposure over 12 months resulted in macrophage in ltration, bronchiolisation of proximal alveoli, and microgranuloma formation. Additionally Everitt et al. and Gelzleichter et al. found in hamsters increased focal pleural thickenings after a 12-week exposure to RCF (17,18).

Symptoms
Data from RCF morbidity in humans indicated that exposed workers suffered from dyspnoe, and showed signi cant de cits in certain measurements in lung function. Also a dose-related increase in pleural plaques was described (3,19).

Trethowan et al. studied 628 current employees in the manufacturer of ceramic bres in seven European
plants in three countries (20). In all plants, the most frequent symptoms of the employees were nasal stiffness in 55% of all subjects, 41% complained of eye irritation, 36% complained of skin irritation, 18% of wheeze, 13% dry cough, and 12% ful lled the criteria of chronic bronchitis. All symptoms were more frequent in current smokers compared with ex or never smokers.

Lung function changes
The longest ongoing observational study by LeMasters et al., 30-year mortality and respiratory morbidity study of refectory bres workers, showed localized pleural thickening associated with small decreases in spirometry results. While statistical signi cance was observed for FVC between cumulative RCF exposure (eg, 15 vs >60 bre-months/cc at age 40), there was no consistent pattern demonstrating increasing loss in FVC with higher exposure category. This was also depended on initial weight and weight gain (p<0.001). Additional FEV1 reduction was associated with cumulative pack-years and current smoking status signi cantly. Weill et al. studied 1,028 male workers from seven RCF-plants, with median employment of 18 years and found no respiratory symptoms or adverse lung function related to exposure (21). In a follow-up, Hughes et al. described higher prevalence (5.9%) of respiratory symptoms in workers compared to 3.1% in a non-exposed healthy population even when adjusted for smoking (22 (23). The observed difference was independent of smoking habits and self-assessed former asbestos exposure. In summary RCF exposures failed to be associated with reduced lung function tests so far.
Pleuralchanges Lockey et al. described a dose response between pleural changes and cumulative ber exposure in RCF workers (2). In RCF production pleural changes increased after a latency > 20 years with an OR of 10.8 [95%-CI: 2.4 -47.9] (2, 24) even without any asbestos exposure. In contrast interstitial changes have not been associated with RCF exposure (25). The occurrence of pleural changes on chest radiographs suggests that RCF has su cient bio persistence to directly or indirectly induce pleural in ammatory response resulting in pleural thickening (26, 27 The new ndings of our case report are besides pleural thickening and calci ed pleural plaques also, the formation of a rounded atelectasis in a RCF worker accompanied with restrictive lung function. Rounded atelectasis is more common in men (80%) than in women. The most common cause of rounded atelectasis (RA) is occupational exposure to asbestos (29,30). The direct mechanism for the development of rounded atelectasis has not been fully explained. According to one of the theories (29), pleural uid causes local atelectasis due to the pressure on the adjacent lung. If the rate of uid pleural accumulation exceeds the absorptive capacity of adjacent alveoli, visceral pleura damage occurs with formation of a ssure and translocation of the lung towards that ssure. As a result of this process, the lung folds in a concentric shape maintained by developing adhesions. When the effusion is resorbed, the lung lls in the space around rounded atelectasis. According to another theory, the lesions are initiated by local pleuritis due to agents, such as asbestos bres. Local accumulation of pleural uid or bre dusts in the course of asbestosis, leads to shrinkage and thickening of pleura. The adjacent lung also shrinks and rounded atelectasis develops (31). Pathophysiological it may be obvious, that not only asbestos bres but also RCF causes rounded atelectasis.

Conclusion
A rounded atelectasis was found in chest CT scans in a middle aged worker in a RCF processing plant during a medical check-up. This is accompanied with a restrictive ventilation disorder and reduced diffusing capacity. Meanwhile the restrictive lung disease is accepted as a recognised occupational disease by the accident insurance institution. A comprehensive lung function analysis and in case of restrictive lung disorders additional CT scans are needed in RCF exposed workers in accordance to the guidelines for medical occupational examinations comparable to asbestos exposed workers.

Declarations
Ethics approval and consent to participate This report does not include studies on humans or animals. The examinations were carried out on behalf of the accident insurance company. The ndings are reported in anonymised form for the conduct of the assessment and quality assurance. An ethical vote for this has not been necessary. The written patient's consent for publication is available.

Consent to publication
Appropriate written informed consent was obtained for publication of this case report.

Availability of data and materials
All data generated or analysed during this study are included in this published article.

Competing interests
The authors declare that they have no competing interests.

Funding
There are no nancial con icts of interest to disclose.
Authors' contributions UB und JS: conception and design, acquisition of data, interpretation of data, writing the manuscript and revised it critically. They have given nal approval of the version to be published. AS contributed with TEM and EDX analysis and interpretation of data substantially. MK revised the manuscript critically and gave nal approval of the version to be published. All authors read and approved the nal manuscript.  Figure 1 p.a. and lateral chest X-ray with an adhered costodiaphragmatic sinus (white arrow). Pleural thickening with brosis strands is seen on the left middle eld.

Figure 2
Axial cross sections of the lung -mediastinal (a) resp. lung window (b). Bilateral diffuse pleural thickening and rounded atelectasis with a "comet tail" sign (thick white arrow) and a reduction in the volume of the left lower lobe. Calci ed pleural plaques (slim white arrow).

Figure 3
Multiplanar reformation (MPR) of computed lung tomography. Pleural thickening with brosis strands on dorsal chest wall (thick white arrows) and pleural calci cations (slim white arrows).  Energy dispersive X-ray spectrum of the RCF F3a as example of aluminium silicate bres. The EDX spectrum shows oxygen, aluminium and silicon peaks resulting from aluminium oxide (Al2O3) and silicon dioxide (SiO2). The Au peak results from a ne layer of gold from the sample preparation.