Comment on 'Limitations in evaluating COVID-19 protective face masks using open circuit spirometry systems: respiratory measurement mask introduces bias in breathing pressure and perceived respiratory effort'.

We comment on the paper by Seibt and coworkers (Seibtet al2023) which investigates whether wearing an additional respiratory measurement mask during open-circuit spirometry assessments (respirometry mask) shows any effect on breathing pressure and perceived respiratory effort when wearing protective face masks commonly worn during the COVID-19 pandemic.

Influence of face masks on the subjective impairment at different physical workloads.

To quantify the subjective and cognitive impairment caused by wearing face masks at work, 20 men and 20 women (median age 47 years, range 19-65) were tested under different ergometer workloads while wearing surgical mask, community mask, FFP2 respirator or no mask in a randomized and partially double-blinded design. Masks were worn also at the workplace for four hours. Subjective impairment was recorded by questionnaires. Cognitive performance was tested before and after the workplace examination. Subjective feeling of heat, humidity, and difficult breathing increased with rising physical exertion and wearing time for all three mask types, most notably for FFP2. Even when blinded, participants with FFP2 reported difficult breathing already at rest. During physical exertion, individuals with low tolerance to discomfort reported significantly stronger impairment (OR 1.14, 95% CI 1.02-1.27). Regarding light work, older subjects (OR 0.95, 95% CI 0.92-0.98) and women (OR 0.84, 95% CI 0.72-0.99) showed significantly lower and atopic subjects stronger impairment (OR 1.16, 95% CI 1.06-1.27). No significant influence of mask wearing was detected on cognitive performance. Wearing a mask had no effect on cognitive performance, but led to discomfort which increased with physical exertion and wearing time. Individuals who tolerate discomfort poorly felt more impaired by wearing a mask during physical exertion.

Effects of wearing different face masks on cardiopulmonary performance at rest and exercise in a partially double-blinded randomized cross-over study.

The use of face masks became mandatory during SARS-CoV-2 pandemic. Wearing masks may lead to complaints about laboured breathing and stress. The influence of different masks on cardiopulmonary performance was investigated in a partially double-blinded randomized cross-over design. Forty subjects (19-65 years) underwent body plethysmography, ergometry, cardiopulmonary exercise test and a 4-h wearing period without a mask, with a surgical mask (SM), a community mask (CM), and an FFP2 respirator (FFP2). Cardiopulmonary, physical, capnometric, and blood gas related parameters were recorded. Breathing resistance and work of breathing were significantly increased while wearing a mask. During exercise the increase in minute ventilation tended to be lower and breathing time was significantly longer with mask than without mask. Wearing a mask caused significant minimal decreases in blood oxygen pressure, oxygen saturation, an initial increase in blood and inspiratory carbon dioxide pressure, and a higher perceived physical exertion and temperature and humidity behind the mask under very heavy exercise. All effects were stronger when wearing an FFP2. Wearing face masks at rest and under exercise, changed breathing patterns in the sense of physiological compensation without representing a health risk. Wearing a mask for 4-h during light work had no effect on blood gases.

No inflammatory effects after acute inhalation of barium sulfate particles in human volunteers.

BACKGROUND: Most threshold limit values are based on animal experiments. Often, the question remains whether these data reflect the situation in humans. As part of a series of investigations in our exposure lab, this study investigates whether the results on the inflammatory effects of particles that have been demonstrated in animal models can be confirmed in acute inhalation studies in humans. Such studies have not been conducted so far for barium sulfate particles (BaSO4), a substance with very low solubility and without known substance-specific toxicity. Previous inhalation studies with zinc oxide (ZnO), which has a substance-specific toxicity, have shown local and systemic inflammatory respones. The design of these human ZnO inhalation studies was adopted for BaSO4 to compare the effects of particles with known inflammatory activity and supposedly inert particles. For further comparison, in vitro investigations on inflammatory processes were carried out. METHODS: Sixteen healthy volunteers were exposed to filtered air and BaSO4 particles (4.0 mg/m3) for two hours including one hour of ergometric cycling at moderate workload. Effect parameters were clinical signs, body temperature, and inflammatory markers in blood and induced sputum. In addition, particle-induced in vitro-chemotaxis of BaSO4 was investigated with regard to mode of action and differences between in vivo and in vitro effects. RESULTS: No local or systemic clinical signs were observed after acute BaSO4 inhalation and, in contrast to our previous human exposure studies with ZnO, no elevated values of biomarkers of inflammation were measured after the challenge. The in vitro chemotaxis induced by BaSO4 particles was minimal and 15-fold lower compared to ZnO. CONCLUSION: The results of this study indicate that BaSO4 as a representative of granular biopersistent particles without specific toxicity does not induce inflammatory effects in humans after acute inhalation. Moreover, the in vitro data fit in with these in vivo results. Despite the careful and complex investigations, limitations must be admitted because the number of local effect parameters were limited and chronic toxicity could not be studied.

Physiological responses, self-reported health effects, and cognitive performance during exposure to carbon dioxide at 20 000 ppm.

In this study, 24 subjects (20-58 years) were exposed to carbon dioxide (CO2 ) at 770 ppm and 20 000 ppm in an exposure laboratory for 4-h, including 2 × 15 min of cycling to investigate the effects on acid-base balance, physiological responses, cognitive performance and acute health. Capillary blood analysis, heart rate, respiratory rate, divided attention, flexibility, and sustained attention from the Test Battery for Attentional Performance (TAP), critical flicker fusion frequency (CFF), and self-reported symptoms were measured before, during, and after the 4-h exposure. Blood pH decreased and partial pressure of carbon dioxide (pCO2 ) increased significantly when exposed to 20 000 ppm CO2 compared to 770 ppm. However, the values remained within the normal range. In addition, respiratory rate increased slightly but significantly at 20 000 ppm CO2 . No significant changes in heart rate, CFF, task performance or acute health were found. In sum, the findings suggest that the observed changes in acid-base balance and ventilation can be classified as physiological adaptation responses. Impairment of cognitive performance is not expected from exposure to 20 000 ppm CO2 , neither as direct effect on central nervous system function nor as a distraction related to perception of health effects.

Health effects after inhalation of micro- and nano-sized zinc oxide particles in human volunteers.

Inhalation of ZnO particles can cause inflammation of the airways and metal fume fever. It is unclear if different sizes of the particles alter these effects. However, various studies report higher biological activity of other nano-sized particles compared to microparticles. No effects at all were observed after inhalation of micro- and nano-sized zinc oxide (ZnO) particle concentrations of 0.5 mg/m3. Studies with different particle sizes of ZnO at higher exposures are not available. Accordingly, we hypothesized that inhalation of nano-sized ZnO particles induces stronger health effects than the inhalation of the same airborne mass concentration of micro-sized ZnO particles. 16 healthy volunteers (eight men, eight women) were exposed to filtered air and ZnO particles (2.0 mg/m3) for 2 h (one session with nano- and one with micro-sized ZnO) including 1 h of cycling at moderate workload. Effect parameters were symptoms, body temperature, inflammatory markers in blood and in induced sputum. Induced sputum was obtained at baseline examination, 22 h after exposure and at the end of the final test. The effects were assessed before, immediately after, about 22 h after, as well as two and three days after each exposure. Neutrophils, monocytes and acute-phase proteins in blood increased 22 h after micro- and nano-sized ZnO exposure. Effects were generally stronger with micro-sized ZnO particles. Parameters in induced sputum showed partial increases on the next day, but the effect strengths were not clearly attributable to particle sizes. The hypothesis that nano-sized ZnO particles induce stronger health effects than micro-sized ZnO particles was not supported by our data. The stronger systemic inflammatory responses after inhalation of micro-sized ZnO particles can be explained by the higher deposition efficiency of micro-sized ZnO particles in the respiratory tract and a substance-specific mode of action, most likely caused by the formation of zinc ions.

Heart rate variability and cardiac repolarization after exposure to zinc oxide nanoparticles in healthy adults.

BACKGROUND: Exposure to airborne zinc oxide (ZnO) particles occurs in many industrial processes, especially in galvanizing and welding. Systemic inflammation after experimental inhalation of ZnO particles has been demonstrated previously, but little is known about the impact on the cardiovascular system, particularly on the autonomic cardiac system and the risk of arrhythmias. In this study we investigated the short-term effects of ZnO nanoparticles on heart rate variability (HRV) and repolarization in healthy adults in a concentration-dependent manner at rest and during exercise in a controlled experimental set-up. METHODS: Sixteen healthy subjects were exposed to filtered air and ZnO particles (0.5, 1.0 and 2.0 mg/m3) for 4 h, including 2 h of cycling at low workloads. Parameters were assessed before, during, immediately after, and about 24 h after each exposure. For each subject, a total number of 46 10-min-sections from electrocardiographic records were analyzed. Various parameters of HRV and QT interval were measured. RESULTS: Overall, no statistically significant effects of controlled ZnO inhalation on HRV parameters and QT interval were observed. Additionally, a concentration-response was absent. CONCLUSION: Inhalation of ZnO nanoparticles up to 2.0 mg/m3 for 4 h does not affect HRV and cardiac repolarization in healthy adults at the chosen time points. This study supports the view that cardiac endpoints are insensitive for the assessment of adverse effects after short-term inhalation of ZnO nanoparticles.

Effectiveness of an on-body lifting aid (HAL® for care support) to reduce lower back muscle activity during repetitive lifting tasks.

The Hybrid Assistive Limb Lumbar Type (HAL) is an active exoskeleton that provides motion according to the wearer's voluntary drive. It was developed to support back muscles during repetitive lifting tasks. The purpose of this paper was to determine if the myoelectric activity of the back muscles is reduced or altered when using the HAL and to investigate a possible influence of its use on the cardiovascular system. Fourteen healthy young men without lower back pain underwent a freestyle, symmetrical-lifting protocol. Participants lifted a 17.05 kg handled-box for 10 min. with and without HAL support. Surface electromyography (sEMG) signals were recorded at thoracic (TES) and lumbar erector spinae (LES) and quadriceps femoris (QF). Heart rate was recorded from electrocardiogram. The subjects rated their level of physical exertion using the Borg Rating of Perceived Exertion (BORG) scale. Additionally they commented on sites of discomfort, perceptions of force, and loss of range of motion. The root mean square and integrated sEMG value was significantly reduced at the LES and TES. Heart rate variability output variables did not show any significant difference. The BORG-Scale showed no difference, with a mean score of 2.5. The HAL decreased the magnitude and onset of muscle activity and force in the lower back in a repetitive lifting task. Reduction of the muscle force and activity required during the lifting process is meaningful regarding lower back pain prevention, and the HAL may contribute to reducing the incidence of lower back pain in the working population.

Airway inflammation after inhalation of nano-sized zinc oxide particles in human volunteers.

BACKGROUND: Workers in the zinc production and processing of galvanized sheet steel are exposed to a complex mixture of particles and gases, including zinc oxide (ZnO) that can affect human health. We aimed to study the effects of short-term controlled exposure to nano-sized ZnO on airway inflammatory markers in healthy volunteers. METHODS: Sixteen subjects (8 females, 8 men; age 19-42, non-smokers) were exposed to filtered air and ZnO nanoparticles (0.5, 1.0 and 2.0 mg/m3) for 4 h, including 2 h of cycling with a low workload. Induced sputum samples were collected during a medical baseline and a final examination and also about 24 h after each exposure. A number of inflammatory cellular and soluble markers were analyzed. RESULTS: Frequency and intensity of symptoms of airway irritation (throat irritation and cough) were increased in some subjects 24 h after ZnO exposures when compared to filtered air. The group comparison between filtered air and ZnO exposures showed statistically significant increases of neutrophils and interleukin-8 (IL-8), interleukin-6 (IL-6), matrix metalloproteinase (MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1) in sputum starting at the lowest ZnO concentration of 0.5 mg/m3. However, a concentration-response relationship was absent. Effects were reversible. Strong correlations were found between neutrophil numbers and concentrations of total protein, IL-8, MMP-9, and TIMP-1. CONCLUSIONS: Controlled exposures of healthy subjects to ZnO nanoparticles induce reversible airway inflammation which was observed at a concentration of 0.5 mg/m3 and higher. The lack of a concentration-response relationship warrants further studies.

Concentration-dependent systemic response after inhalation of nano-sized zinc oxide particles in human volunteers.

BACKGROUND: Inhalation of high concentrations of zinc oxide particles (ZnO) may cause metal fume fever. In an earlier human inhalation study, no effects were observed after exposure to ZnO concentrations of 0.5 mg/m3. Further data from experimental studies with pure ZnO in the concentration range between 0.5 and 2.5 mg/m3 are not available. It was the aim of this experimental study to establish the concentration-response relationship of pure nano-sized ZnO particles. METHODS: Sixteen healthy subjects were exposed to filtered air and ZnO particles (0.5, 1.0 and 2.0 mg/m3) for 4 h on 4 different days, including 2 h of cycling with a low workload. The effects were assessed before, immediately after, and about 24 h after each exposure. Effect parameters were symptoms, body temperature, inflammatory markers and clotting factors in blood, and lung function. RESULTS: Concentration-dependent increases in symptoms, body temperature, acute phase proteins and neutrophils in blood were detected after ZnO inhalation. Significant effects were detected with ZnO concentrations of 1.0 mg/m3 or higher, with the most sensitive parameters being inflammatory markers in blood. CONCLUSION: A concentration-response relationship with nano-sized ZnO particles in a low concentration range was demonstrated. Systemic inflammatory effects of inhaled nano-sized ZnO particles were observed at concentrations well below the occpational exposure limit for ZnO in many countries. It is recommended to reassess the exposure limit for ZnO at workplaces.

Correction to: Quantification of N-phenyl-2-naphthylamine by gas chromatography and isotope-dilution mass spectrometry and its percutaneous absorption ex vivo under workplace conditions.

The article 'Quantification of N-phenyl-2-naphthylamine by gas chromatography and isotope-dilution mass spectrometry and its percutaneous absorption ex vivo under workplace conditions' written by Heiko Udo Käfferlein, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 12th September 2017 without open access.

Quantification of N-phenyl-2-naphthylamine by gas chromatography and isotope-dilution mass spectrometry and its percutaneous absorption ex vivo under workplace conditions.

N-Phenyl-2-naphthylamine (P2NA) is an antioxidant used to protect rubbers from flex-cracking. P2NA can be converted in vivo to 2NA, one of the most potent bladder carcinogens. Here, we report the specific and ultra-sensitive quantification of P2NA in the receptor fluid of Franz diffusion cells by gas chromatography and isotope-dilution tandem-mass spectroscopy (GC-MS/MS). The experimental conditions were optimized to minimize losses of P2NA due to surface absorption on glass, plastic, and rubber material, and subsequently validated. Static and dynamic diffusion cell conditions were used to study the percutaneous penetration of P2NA into freshly prepared porcine skin. The experimental settings closely resembled those of the printing industry in the 1960s/1970s in Germany where P2NA-containing solutions in dichloromethane have been used. P2NA penetrated the skin at very low levels (0.02 ± 0.01 µg/cm2/h) with a cumulative penetrated amount of 0.80 ± 0.26 µg/cm2, a lag time of 6.33 ± 2.21 h and under dynamic conditions. Compared to the receptor fluid, 10-40-fold higher concentrations were found in the skin, predominantly in the dermis and the stratum corneum. Dichloromethane acted as a penetration enhancer by increasing the cumulative penetrated amounts and the recovery of P2NA in both the receptor fluid and the skin, while shortening its lag time. However, the flux remained unaffected. Due to its accumulation in subcutaneous layers, we finally proved that P2NA is continuously released into the receptor fluid despite exposure cessation up to 160 h. Overall, the results show that close attention has to be paid to dermal absorption of P2NA in exposed workers.

Serial measurements of exhaled nitric oxide at work and at home: a new tool for the diagnosis of occupational asthma.

Whereas serial measurements of lung function at work and at home are a well-known diagnostic tool for the diagnosis of occupational asthma (OA), little is known about the serial measurements of non-invasive parameters such as exhaled nitric oxide (eNO). A 51-year-old baker with variable shortness of breath without relation to work was examined for suspected OA. Skin prick test showed weak sensitizations to wheat and rye flour (without sensitizations to environmental allergens) that were corroborated by in vitro testing (CAP class 3). Baseline FEV1 of 58% predicted and a decrease of forced expiratory volume in 1 s (FEV1) after placebo (sugar powder) of 17% did not allow inhalational challenge testing. The patient performed daily measurements of FEV1 and eNO for about a month during a holiday at home and at work. Whereas symptoms and FEV1 did not show differences between holidays and work periods, eNO showed a clear increase from below 10 ppb to a maximum of 75 ppb. A diagnosis of baker's asthma was made, and the patient quit his job immediately after medical advice. A year afterwards, the patient was still taking asthma medication, but his symptoms had improved, FEV1 had increased to 73% predicted, and eNO was 25 ppb. We conclude that serial measurements of eNO at home and at work may be a useful tool for the diagnosis of OA.

Human exposure to airborne aniline and formation of methemoglobin: a contribution to occupational exposure limits.

Aniline is an important starting material in the manufacture of polyurethane-based plastic materials. Aniline-derived methemoglobinemia (Met-Hb) is well described in exposed workers although information on the dose-response association is limited. We used an experimental design to study the association between aniline in air with the formation of Met-Hb in blood and the elimination of aniline in urine. A 6-h exposure of 2 ppm aniline in 19 non-smoking volunteers resulted in a time-dependent increase in Met-Hb in blood and aniline in urine. The maximum Met-Hb level in blood (mean 1.21 ± 0.29 %, range 0.80-2.07 %) and aniline excretion in urine (mean 168.0 ± 51.8 µg/L, range 79.5-418.3 µg/L) were observed at the end of exposure, with both parameters rapidly decreasing after the end of exposure. After 24 h, the mean level of Met-Hb (0.65 ± 0.18 %) returned to the basal level observed prior to the exposure (0.72 ± 0.19 %); whereas, slightly elevated levels of aniline were still present in urine (means 17.0 ± 17.1 vs. 5.7 ± 3.8 µg/L). No differences between males and females as well as between slow and fast acetylators were found. The results obtained after 6-h exposure were also comparable to those observed in four non-smoking volunteers after 8-h exposure. Maximum levels of Met-Hb and aniline in urine were 1.57 % and 305.6 µg/L, respectively. Overall, our results contribute to the risk assessment of aniline and as a result, the protection of workers from aniline-derived adverse health effects at the workplace.