key: cord-0727323-9vneo8ib
authors: Perna, Giampaolo; Cuniberti, Francesco; Daccò, Silvia; Nobile, Maria; Caldirola, Daniela
title: Impact of respiratory protective devices on respiration: implications for panic vulnerability during the COVID-19 pandemic.
date: 2020-09-07
journal: J Affect Disord
DOI: 10.1016/j.jad.2020.09.015
sha: b359dd1de19b5fd178978d6a95fba92d17d2f814
doc_id: 727323
cord_uid: 9vneo8ib

BACKGROUND: The wearing of respiratory protective devices (RPDs) correctly and continually in situations where people are at risk of respiratory infections is crucial for infection prevention. Certain people are poorly compliant with RPDs due to RPD-related annoyance, including respiratory discomfort. We hypothesized that individuals vulnerable to panic attacks are included in this group. No published studies on this topic are available. The evidence for our hypothesis was reviewed in this study as a starting point for future research. METHODS: We selected a set of experimental studies that measured the respiratory physiological burden in RPD wearers through objective and validated methods. We conducted a bibliographic search of publications in the PubMed database (January 2000–May 2020) to identify representative studies that may be of interest for panic respiratory pathophysiology. RESULTS: Five studies were included. Wearing RPDs exerted significant respiratory effects, including increased breathing resistance, CO(2) rebreathing due to CO(2) accumulation in the RPD cavity, and decreased inhaled O(2) concentration. We discussed the implications of these effects on the respiratory pathophysiology of panic. LIMITATIONS: Most studies had a small sample size, with a preponderance of young participants. Different methodologies were used across the studies. Furthermore, differences in physical responses between wearing RPDs in experimental settings or daily life cannot be excluded. CONCLUSIONS: This research supports the idea that panic-prone individuals may be at higher risk of respiratory discomfort when wearing RPDs, thereby reducing their tolerance for these devices. Strategies to decrease discomfort should be identified to overcome the risk of poor compliance.

Furthermore, the most recent recommendations of the World Health Organization and the US Centers for Disease Control and Prevention (CDC) include the wearing of face masks by the general public among the strategies for mitigating the risk and impact of COVID-19 (CDC, 2020) .

The most used RPDs among HCWs and the general population are surgical facemasks (SMs) and filtering facepiece respirators (FFRs), which include N95 (American standard, CDC), FFP2 (i.e., the closest European equivalent to N95), and FFP3 masks (Baig et al., 2010; Wizner et al., 2018) .

The correct and continual wearing of RPDs is crucial in situations where people are at risk of respiratory infections. To date, the use of RPDs is mandatory among HCWs in Italy, as per the guidelines for HCWs of the Lombardy Region (Regione Lombardia, 2020a) , while it is mandatory or highly recommended, depending on the context, among the general population, as per Regional

Ordinance No 314 of 03/21/2020 and subsequent inclusions and modifications of the Lombardy Region guidelines (Regione Lombardia, 2020b) . As psychiatrists and psychologists who are experts in anxiety disorders and work in Northern Italy, one of the areas most affected by the COVID-19 pandemic, we have observed significant difficulties in our patients when wearing RPDs because of physical symptoms and discomfort. In our current clinical experience, patients suffering from panic attacks (PAs) or panic disorder (PD) are the most afflicted by physical symptoms, mainly respiratory, related to the use of RPDs. During psychiatric visits at our facilities, they often complain about these symptoms and ask for permission to move or remove their RPDs, and they report similar symptoms that lead urgency in moving or removing the devices in their daily life.

Unfortunately, being poorly compliant in RPD use may increase their risk of contracting COVID-19 (CDC, 2020) . Moreover, many patients worry that their discomfort could become evident to others who may judge them for moving their RPDs or even for their urgency in removing the devices while in social contexts where removal is not recommended. This concern may worsen social avoidance and agoraphobia, two conditions often associated with PD.

In line with our experience, some studies revealed that certain people in the general population appeared to repeatedly move their masks, touch them, or not to wear them when required due to multiple physiological and psychological sources of RPD-related discomfort, thereby decreasing infection prevention. For the same reasons, even HCWs, a category of people who are supposed to be well trained on this issue, were often found to be poorly compliant with RPDs (Baig et al., 2010; Johnson, 2016; Wizner et al., 2018) . Respiratory discomfort is a main complaint of RPD wearers, and it was found that approximately 30% of HCWs complained of breathing difficulties most of the time or always when wearing an N95 respirator. A further 34% of HCWs declared difficulty breathing some of the time, while 36% never or rarely complained of breathing difficulties (Baig et al., 2010) . In line with this, increased levels of anxiety related to a sense of claustrophobia have been described by the wearers of different RPD types (Baig et al., 2010; Johnson, 2016) .

Although limited, these findings suggest that the degree of respiratory discomfort varies considerably among wearers. Since wearing RPDs may induce a real burden of respiratory effects, it is conceivable that the levels of subjective respiratory and emotional responses arise from the interplay between the physiological effects of RPDs and the individual's sensitivity to them. Driven by our current clinical observations and based on the well-established panic-respiration connection, we hypothesized that individuals with vulnerability to PAs, with or without full-blown PD, can be included among RPD wearers at risk of high respiratory discomfort. Experimental evidence has supported the hypothesis, unique in the realm of mental disorders, that subclinical alterations of basic physical functioning, mainly of the respiratory system, may be involved in the pathogenesis of PAs (Caldirola and Perna, 2019) . Although the source of these features remains unclear and required further discussion, patients with PD, from a clinical point of view, experience a significant burden of respiratory and physical symptoms or discomfort during PAs, as well as in several environmental situations. Furthermore, the fear of suffocation is one of their primary fears, and they usually develop attentional bias toward somatic sensations, proneness to catastrophic misinterpretation of normal bodily changes, and interoceptive/exteroceptive conditioned responses.

Finally, some authors proposed that the fear and concerns about somatic sensations may be even more pronounced in those patients with PD patients who present alexithymia (De Berardis et al., 2013 , 2007 . Overall, patients with PD seem to exhibit greater physical and emotional difficulties in coping with somatic sensations and internal bodily changes compared with individuals suffering from other anxiety disorders (Hoehn-Saric et al., 2004; Rudaz et al., 2010) .

To date, there is a lack of studies evaluating the subjective or objective impact of wearing RPDs in individuals with PAs or PD. This brief narrative review provides an empirical starting point for future research on this topic. It summarizes the main respiratory effects of common RPDs and discusses their implications on the pathophysiology of individuals vulnerable to panic. We conducted a bibliographic search of the PubMed database for articles published between January 2000 and May 2020 that aimed to measure the respiratory physiological burden in RPD wearers.

We used the following keywords in combination: respirator(s), face mask(s), respiration, breathing, resistance, ventilation, CO 2 , carbon dioxide, O 2, and oxygen. We aimed to select representative studies that may be of interest for panic respiratory pathophysiology. We selected four representative studies that satisfied the inclusion criteria of providing objective measurements of respiratory parameters measured using validated methods of recordings and calculations in healthy individuals (i.e., without medical diseases) aged ≥18 years when wearing RPDs. We also included one study performed using a computational breathing simulation, as representative of the body of research that investigated the impact of RPDs on physiological functions using computerized devices and techniques without human subjects (Table 1) .

The four selected studies that collected objective measures in healthy individuals wearing RPDs (N95 FFRs or full facepiece respirators) revealed some significant respiratory effects, both in those who were experienced with wearing these devices (Laferty and McKay, 2006; Lee and Wang, 2011 ) and those who were not (Roberge et al., 2010; Smith et al., 2013) , and this was also found by (Zhang et al., 2016) using a computational fluid dynamics simulation of full breathing cycles. Table   1 reports a detailed description of the studies, including the sample characteristics, procedures, and main results of interest. Overall, RPDs may alter the users' natural breathing patterns and make breathing more difficult.

Firstly, an increase in breathing resistance was found, with percentage increments in expiratory and inspiratory flow resistance reaching up to approximately 300% (Lee and Wang, 2011; Zhang et al., 2016) . This increment may induce a significant increase in respiratory effort to overcome resistance and maintain adequate expiratory flow rates (Lee and Wang, 2011; Zhang et al., 2016) . It may also lead to hypoventilation, as suggested by the average decrease of 37% in air exchange volume found in N95 FFR wearers by (Lee and Wang, 2011). The increased breathing resistance, in association with CO 2 rebreathing while wearing RPDs (see below), may amplify respiratory fatigue and impair physical work capacity (Smith et al., 2013) . However, although most results pointed to an increase in breathing resistance while wearing RPDs, the range of resistancerelated respiratory values varied widely both across studies and across participants in the same study. Furthermore, (Roberge et al., 2010) did not observe indications of increased respiratory effort in RPD wearers when assessed at very low workload for a relatively brief period of time. This variability suggests that a pronounced subjective diversity in respiratory sensitivity may exist in individuals wearing RPDs and that certain conditions (e.g., higher workloads, during speech, or prolonged periods of RDP use) may exert a greater impact on respiration than others.

Secondly, facepiece dead volume (i.e., the void between the respirator and the face) accumulates exhaled CO 2 , which is inhaled during the next inspiration. Hence, the dead volume, in association with hypoventilation related to increased breathing resistance, can contribute to CO 2 rebreathing while wearing FFRs., Dead space CO 2 accumulation in individuals wearing RPDs during common conditions, such as at rest, during speech or at low work rates, ranged from ≥1.5% to approximately 3% in the reviewed studies. This is up to 100 times higher than that expected in normal environmental air (0.03%-0.04%) and well beyond the recommended CO 2 thresholds in the workplace environment (i.e., 0.5%, averaged over an 8-h work day) or in respirators' microenvironment when testing RPDs (i.e., CO 2 should not exceed 1% for more than 1 consecutive minute), as indicated by the guidelines of several regulatory organizations (details in Table 1 ). It is well known that a prolonged exposure to 2%-3% CO 2 may generate headache, sweating, dizziness, and dyspnea, even in individuals without medical diseases (Johnson, 2016).

Finally, the increased RPD-related dead space was found to lower the average inhaled O 2 concentration. (Laferty and McKay, 2006) and (Roberge et al., 2010) found O 2 levels inside respirators' cavities ranging from 16.6% to 18.3%, which represent an O 2 -deficient space, according to the recommended threshold of the Occupational Health and Safety Administration (O 2 deficiency is an atmosphere that contains <19.5% O 2 by volume) ( Table 1 ). The decreased O 2 levels may result in a faster transition from aerobic to anaerobic respiration, lower tolerance for physical exertion, and decreased working capacity (Laferty and McKay, 2006) . It should be noted that despite the decrease in O 2 % in the RPD cavity, no impact on blood oxygen saturation (SpO 2 ), as measured via pulse oximetry, was found in both the abovementioned studies. This discrepancy could plausibly be related to a brief period of RPD use during low energy expenditure, as suggested by a study that found a significant decrease in SpO 2 in surgeons wearing SMs only during procedures longer than 1 h (Beder et al., 2008) and another reporting a significant decline of arterial partial pressure of O 2 in patients wearing N95 FFRs after 4 h of hemodialysis (Kao et al., 2004) .

Considering the pathophysiology of panic, these RPD respiratory effects may have a peculiar and relevant impact on vulnerable individuals. Patients with PD were thought to have a hyperactive suffocation alarm, which results in a specific behavioral and respiratory hypersensitivity to hypercapnia (Klein, 1993) . Different laboratory challenges inducing hypercapnia, such as the Read rebreathing technique, the prolonged inhalation of 5% or 7% CO 2 -enriched air, or the double inhalation of a 35% CO 2 /65% O 2 gas mixture, induce significantly higher rates of PAs, with pronounced respiratory symptoms in patients with PD compared with control groups (Caldirola and Perna, 2019; Gorman et al., 1997; Leibold et al., 2016; Okuro et al., 2020; Perna et al., 1999) .

Similarly, individuals who experienced PAs without developing full-blown PD and healthy firstdegree relatives of patients with PD displayed greater likelihood of panic symptoms and respiratory-response abnormalities during hypercapnic challenges than the control group (Caldirola and Perna, 2019) . Moreover, patients with PD are hypersensitive to other laboratory respiratory challenges, such as breath-holding, hyperventilation, or a hypoxic challenge test (Beck et al., 1999; Caldirola and Perna, 2019; Okuro et al., 2020) . They suffer from irregular breathing patterns, impaired diaphragmatic breathing with reduced vital capacity, chronic hyperventilation, and a common sensation of difficulty in breathing during daily life activities (Caldirola and Perna, 2019; Grassi et al., 2013) . Hence, it is conceivable that the inhalation of increased CO 2 concentrations while wearing RPDs may elicit respiratory discomfort, a sense of suffocation, and panic symptoms to a larger extent in panic-prone individuals than in others. They may also be more sensitive to increased breathing resistance and decreased concentrations of inhaled O 2 than nonpanic-prone individuals, resulting in greater breathing effort, dyspnea and physical fatigue, even during mild physical activity. The greater-than-expected associations between PD and asthma/chronic obstructive pulmonary disease (Goodwin and Eaton, 2003; Hasler et al., 2005) may further increase the risk of RPD-related respiratory and physical discomfort in panic-prone individuals.

The use of RPDs has also been associated with other physiological effects, such as disturbances in visual performance, which is thought to cause disorientation in the environment.

Other effects include increased air temperature in the RPD cavity (up to approximately 32°C-33°C) with sweat accumulation, which may add a further burden to breathing and general discomfort (Johnson, 2016; Zhang et al., 2016) . Individuals vulnerable to panic exhibited higher postural instability and dizziness when exposed to unusual patterns of visuo-vestibular interactions and imbalanced autonomic regulation with reduced heart rate variability (Caldirola et al., 2011; Caldirola and Perna, 2019; Coelho and Balaban, 2015; Zhang et al., 2020) . Thus, these individuals may also be more sensitive to the additional non-respiratory and physiological burdens related to FFR use.

This research presents some limitations. Despite the extensive use of the RPDs, the body of research studying the objective physiological impact of wearing these devices was relatively limited. Most studies included small samples, with a preponderance of young participants, thereby limiting the generalizability to other populations. Furthermore, different methodologies and experimental conditions were used across studies, which may explain some differences in results.

Finally, as the studies were conducted in laboratory settings, the ecological validity of the results is not clear-cut, and possible differences between results obtained in experimental settings and physical responses when wearing RPDs in daily life cannot be excluded.

Taking these limitations into consideration, this research supports the idea that individuals vulnerable to panic may be at higher risk of relevant discomfort while wearing RPDs, thereby reducing their tolerance for these devices, as we have observed in our current clinical practice. For this reason, these individuals may be poorly compliant in their use, increasing their risk of contracting COVID-19. Therefore, a "panic fitness" evaluation for the use of respirators should be considered in different settings, including the workplace, and strategies to decrease discomfort should be identified to increase the rate of compliance. It is noteworthy that in some questionnaires used in the process of medical clearance prior to respirator use, screening for the presence of claustrophobia, a condition often associated with PAs and PD, has been included (Desautels et al., 2016; Pappas et al., 1999) . Example strategies to increase compliance in individuals vulnerable to panic may include repeated recovery periods in safe conditions during which RPDs are not used and a personalized approach to workload based on the respirator tolerance of individuals. Moreover, the most suitable type of RPDs should be chosen for panic-prone individuals, while remaining within safety recommendations based on the context in which the devices are used and the level of risk.

For example, the physiological effects of RPDs described above refer to the use of FFRs, while preliminary results show that compared with N95 FFRs, SMs resulted in a lower absolute humidity inside the mask and were associated with a lower subjective perception of humidity, heat, breathing resistance, and overall discomfort (Li et al., 2005) . Thus, SMs may be more tolerable for individuals vulnerable to panic, although further studies on the physiological effects of SMs are needed for confirmation. Furthermore, novel N95 FFRs with micro fans or elastomeric respirators with breathing system filters, might be useful alternatives because these devices are able to better maintain physiological CO 2 levels during use (Goh et al., 2019; Liu et al., 2020) .

RPDs and panic. However, considering the ongoing COVID-19 pandemic and the substantial prevalence of panic vulnerability [the prevalence of PD is approximately 3.8% in the US and European general population, while that of subthreshold panic is similar or even higher (Kessler et al., 2012) ], this issue is worthy of consideration for its potential impact on public health.

The authors declare no funding. 

Health care workers' views about respirator use and features that should be included in the next generation of respirators

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Investigation of the flow-field in the upper respiratory system when wearing N95 filtering facepiece respirator

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CO2= carbon dioxide; CDF= computational fluid dynamic; EV=exhalation valve; Full-FR= Full Facepiece Respirator; HCWs=healthcare workers; N95 FFR= N95 filtering facepiece respirator

Occupational Safety and Health Administration; O2=oxygen

Percentage of mixed inspired CO2; PECO2= Percentage of mixed expired CO2; QLFT= respirator qualitative fit test; QNFT=respirator quantitative fit test

SD=standard deviation; SE= standard error of the mean; VO2= rate of oxygen uptake

s head and shoulders while he/she wears a respirator

Standard set of exercises recommended by Occupational Safety and Health Administration (OSHA) for fit testing: normal breathing, deep breathing, turning head side to side, moving head up and down, talking, bending over (or jogging), and grimace (smile or frown

The recommended OSHA Permissible Exposure Limit (PEL) and the American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value is 0.5% CO2 in workplace atmosphere [averaged over an 8-hour workday (time-weighted average or TWA)] to minimize the potential for asphyxiation and undue metabolic stress

minutes) exposure periods (STEL, short term exposure limit) is recommended by the ACGIH. The ACGIH and the National Institute of Safety and Health (NIOSH) consider a 30-minute exposure to 4% CO2 in ambient atmosphere as dangerous for health. The OSHA definition of O2 deficiency is an atmosphere that contains less than 19

OSHA (1910.134 -"Respiratory Protection

The authors would like to thank Enago (www.enago.com) for the English language review.

All other authors declare that they have no conflicts of interest.