How Patients With Amyotrophic Lateral Sclerosis Perceive Respiratory Interventions

Abstract

Background and Objectives

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that commonly leads to respiratory failure. Early respiratory interventions that may improve symptoms and outcomes are underused when prescribed. We sought to characterize patient perspectives and preferences for respiratory care to enable identification of implementation strategies to improve the uptake of ALS respiratory interventions.

Methods

A prospective multicenter mixed-methods observational study was conducted using semistructured interviews of participants recently diagnosed with ALS at 4 academic centers in the United States. Eligible patients were those with an ALS diagnosis in the previous 12 months, forced vital capacity <80% predicted normal, or presence of dyspnea or orthopnea.

Results

Twenty-four patients with ALS were interviewed. Ten participants were using some form of respiratory therapy, including 8 using noninvasive ventilation (NIV). The most endorsed factors related to openness to initiate respiratory therapy were a doctor's recommendation and abnormal pulmonary function test results. The most commonly endorsed preferences for learning about a respiratory device included kinesthetic and reading. Descriptions of lung volume recruitment were received with more openness than of NIV. For those not prescribed NIV, reasons for hesitancy to start NIV included fear of mask discomfort, claustrophobia, and lack of perceived benefit. Perceptions about NIV differed in participants identifying as “proactive” rather than “reactive” with their health.

Discussion

Patients in the first year after ALS diagnosis have variable receptiveness to respiratory care. These patients place different weights on the factors supporting NIV and may have different educational needs about respiratory interventions. Implementation strategies for respiratory care interventions in ALS should consider patients' motivations for adopting interventions such as NIV, provide multiple educational formats, and identify barriers to incorporating home respiratory care.

Introduction

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that commonly leads to respiratory muscle weakness and ultimately respiratory failure as the most common cause of death.^1-3 Many individuals with ALS develop respiratory impairment within 12 months of diagnosis, which offers a critical window for introducing respiratory care. Respiratory therapies such as lung volume recruitment (LVR), noninvasive ventilation (NIV), and mechanical insufflation-exsufflation may improve respiratory mechanics, symptom burden, quality of life, and survival.^4-7

Despite the burden of respiratory morbidity in ALS, there is uneven uptake of respiratory therapies. As a low-cost respiratory intervention, LVR has been used at all stages of disease and has demonstrated short-term improvement in forced vital capacity (FVC), peak cough flow, and lung compliance.^8-10 Despite the benefits of these therapies, LVR is used sparingly in the United States.

On developing respiratory insufficiency, patients are recommended to use NIV as a method for improving quality of life and survival in ALS.^6,7,11 Retrospective cohorts have demonstrated that fewer than half of patients with ALS use NIV.⁶ Studies of NIV in end-stage ALS show considerable practice variability, likely caused by complex moral, cultural, and ethical beliefs.^12-14

While there is a clear gap between the patients eligible for NIV in ALS and the number that use it, there is insufficient scientific evidence regarding ALS patient perspectives on NIV. Without this knowledge, interventions to improve the uptake of NIV in early ALS may not be successful. The purpose of this study was to use a theory-informed mixed-methods approach to understand ALS patient perspectives on initiating respiratory care. Specifically, we sought to understand patients' motivations to use LVR and NIV, lived experiences with respiratory care, factors influencing their decision making about NIV, and their preferences related to learning about new respiratory care modalities. The long-term goal of this work was to identify and test implementation strategies to increase the use of evidence-based respiratory care in ALS.

Methods

Study Design and Study Population

We performed a prospective cohort interview study of participants diagnosed with ALS at the University of Pennsylvania (UPenn), Thomas Jefferson University (Jefferson), Temple University (Temple), and Penn State University (Penn State) between June 9, 2022, and November 27, 2023 (Pennsylvania ALS (PALS) Cohort Study). We performed simultaneous collection of qualitative (QUAL) and quantitative (quan) data (QUAL + quan mixed-methods design) to explore patient perspectives on respiratory care interventions.¹⁵ The Consolidated Criteria for Reporting Qualitative Research was used to guide reporting in this article.¹⁶

Standard Protocol Approvals, Registrations, and Patient Consents

The study was reviewed and approved by the Institutional Review Board at the UPenn (protocol #834734). All participants provided written informed consent for clinical data collection in this study. The UPenn Institutional Review Board determined that verbal consent was sufficient for participation in and recording of the semistructured interview.

Eligibility and Recruitment

Participants were diagnosed with ALS by an attending neurologist with reference to the World Federation of Neurology revised El Escorial criteria.¹⁷ Beyond acquiring a new diagnosis of ALS within the 12 months preceding the interview, eligible participants were required to be at least 18 years of age, fluent in English, and able to speak intelligibly; have a FVC <80% predicted normal according to 2022 Global Lung Function Initiative race-neutral equations¹⁸; or have evidence of respiratory symptoms as defined by either (1) ALS Functional Rating Scale-Revised (ALSFRS-R) dyspnea score <4 or (2) ALSFRS-R orthopnea scale score <4.¹⁹ Patients were excluded if they had cognitive impairment that would preclude ability to cooperate with the interview. Caregivers were permitted to join the interview if the patient consented.

Eligible individuals provided written informed consent for participation in PALS and for clinical data collection. At the time of consent, participants were asked about their interest in participating in a 30-minute semistructured interview performed by research staff at the UPenn. We contacted a subset of those indicating interest in an interview. As is conventional in exploratory qualitative research, we used purposive sampling to ensure breadth of participant perspectives. We sought to achieve diversity (although not necessarily balance) across the following characteristics: sex, race, ethnicity, and site of symptom onset (i.e., limb vs bulbar).

Instrument Development and Refinement

We created a semistructured interview guide for this study. The semistructured design allowed comparison of key concepts across participants while capturing emic (i.e., in the patient's own words) descriptions of managing their health and factors affecting their perspectives on respiratory care in ALS. Given the objective to inform future implementation efforts, we developed the initial list of questions using the Behaviour Change Wheel²⁰ and the Theoretical Domains Framework. We further sought to understand life stressors, symptom burden, reactions to descriptions of respiratory therapies (i.e., LVR and NIV), triggers for agreeing to start respiratory therapy, and learning style preferences. We collected several demographic characteristics to contextualize the participants' responses. These characteristics included age, patient-identified sex, patient-identified race and ethnicity, and marital status.

Participants were compensated for their participation. We pilot tested the interview guide with 5 patients with ALS to ensure question clarity, and their answers were excluded from the final sample. During the interview study, we refined the interview instrument to explore emerging themes, such as the participants' self-identification as “proactive” or “reactive” with respect to their health. We also introduced a closed-ended, Likert-style question about the likelihood of agreeing to start a new respiratory treatment according to specific methods of introduction. The final interview instrument is provided in eAppendix 1.

The target interview length was 30 minutes to avoid fatiguing participants. The target sample size was 20–30 interviews, based on previous literature supporting the number of sufficient interviews for thematic saturation.^16,21 Interviews were digitally recorded and professionally transcribed.

Data Collection

Interviews were scheduled at the participants' convenience outside of their regularly scheduled clinical visits. Semistructured interviews were completed through video teleconference or telephone according to the participants' preference. All participants completed the interview while at home. At the beginning of the interview, participants were given details about the study before providing verbal consent. Semistructured interviews were performed by research staff of the Penn Mixed Methods Research Lab (D.B.), who were not part of the patient's clinical care team and had no previous relationship with the patient. No repeat interviews were conducted, and transcripts were not returned to participants for comment or correction. Participants did not provide feedback on findings. Interviews occurred until interview themes converged and reached saturation.

Qualitative Analysis

Qualitative analysis was guided by a qualitative descriptive approach to data collection and analysis.^21,22 Three team members independently annotated a subset of transcripts to generate codes. Initial codes were formalized into a codebook and reviewed by the other team members involved in annotation.²³ We managed coding with NVivo 1.7.1 (QSR International). Using the codebook, 2 staff members performed rounds of double coding, each consisting of 5 randomly selected transcripts. Codes were compared by 3 research staff members. Discrepancies were resolved through discussion and consensus. D. Bracy then coded all remaining transcripts. During the coding process, the codebook was revised to clarify ambiguities, eliminate redundancies, and capture missing themes. Using a constant comparative approach, all codebook revisions were applied to previous coding.

Once initial coding was complete, 2 research staff performed focused coding, identifying those codes most pertinent to our research question and connections between them.^24,25 Finally, D. Bracy, J. Ackrivo, and M.B. Lane-Fall undertook explanation development and theme elaboration in an abductive process by positioning explanations for patterns identified through coding, inductively examining these potential explanations to assess their degree of support from our data, and iteratively revising until we arrived at an explanation best supported by our findings.^26,27 To help identify possible implementation strategies to support the uptake of NIV, we categorized each code by COM-B elements such as the social, physical, reflective, automatic, and psychological influences on capability, opportunity, and motivation.²⁰ We then also categorized each code by a Theoretical Domains Framework (TDF) domain (eTable 1).²⁰

Quantitative and Mixed-Methods Analysis

Clinical data were collected during routine clinical visits at participating sites. Clinical data elements of relevance to this study were recorded into a Research Electronic Data Capture database hosted at the UPenn.^28,29

We analyzed quantitative information from clinical sources and our interviews using descriptive statistics. For this study, the purpose of analyzing quantitative data was to provide context about participants' responses and to allow the comparison of findings and characteristics across groups. This use of quantitative data is consistent with using mixed methods for complementarity, in which qualitative and quantitative methods are used to answer related questions (e.g., “How do perspectives on NIV differ by whether participants currently use NIV?“).¹⁵ We conducted our quantitative analysis using Stata 18 (College Station, TX: StataCorp limited liability company). Quantitative data are reported using means and standard deviations or medians and interquartile ranges, as appropriate. Percentages are not provided, given the purposive nature of participant sampling.

Data Availability

Deidentified participant data can be made available by request to the corresponding author. Requests will be considered after planned analyses and reporting have been completed by the investigators. Access will require submission of a protocol that is approved by a review committee and a signed data access agreement.

Results

Approximately 100 charts were screened, and 45 patients with ALS met inclusion criteria. We approached all 45 who met inclusion criteria, and 13 declined to participate. Of the 32 who agreed to participate, we reached thematic saturation by consensus of the coding team after interviewing 24 participants.

The average age at diagnosis was 63 ± 12 years (Table 1). Eleven of the 24 participants were female, most self-identified as White race (n = 21), and none were of Hispanic or Latino ethnicity. Most participants were married or living with a partner (n = 21).

Table 1.

Cohort Characteristics at Time of the Interview (N = 24)

Variable
Age at diagnosis, y	63 ± 12
Female sex, n	11
Race
White	22
Black	2
Ethnicity
Non-Hispanic or non-Latino	24
Marital status
Married/living with partner	21
Widowed	2
Never married	1
Diagnosis delay, y	0.9 (0.6–1.3)
Symptom onset site, n
Limb	22
Bulbar	2
Forced vital capacity % predicted	79 ± 17
Current respiratory therapy
NIV only	6
Breathing exercises only	2
NIV + MI-E only	1
NIV + MI-E + nebulizer	1
None	14
ALSFRS-R total score	38 ± 5
ALSFRS-R dyspnea score, n
4	10
3	10
2	4
ALSFRS-R orthopnea score, n
4	16
3	3
2	2
1	2
0	1
Coronary artery disease, n	4
Obstructive sleep apnea, n	2
Diabetes mellitus, n	5
Hypertension, n	11

Abbreviations: ALSFRS-R = Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised; MI-E = mechanical insufflation-exsufflation; NIV = noninvasive ventilation.

Data are mean ± SD or median (25th percentile - 75th percentile).

The median time between symptom onset and ALS diagnosis, or “diagnosis delay,” was 0.9 (IQR, 0.6–1.3) years. Twenty-two of 24 participants had limb-onset ALS. The mean FVC was 79% ± 17% predicted. There was relatively even balance of people who had started some type of respiratory care regimen (n = 10) vs those who had not (n = 14).

Several themes emerged regarding participant perspectives on respiratory care, and example quotes are summarized in Table 2. Recurring themes included refusal of breathing treatments, proactive vs reactive approaches to health, likelihood of starting a respiratory care treatment, response to descriptions of breathing therapies, experience thus far with respiratory care, learning style preferences, and presence and perceived burden of caregivers.

Table 2.

Representative Quotes From Emergent Themes

Theme		Example quote
Refusal of breathing treatments	Lack of anticipated benefit	“Q: Have they discussed any of the breathing treatments that are available with you yet?”
		Participant: “Yes. Yes. Anything for at night like I figured what it's called like a CPAP [continuous positive airway pressure] machine or whatever. They fully offered and people contacted me and I said I didn't feel like I needed that at this time so I wasn't going to do that.” (participant 1007, man not on respiratory therapy)
		“Q: Has your doctor discussed any breathing treatments with you?”
		Participant: “Yeah but, I don't like to touch on because, I don't need it right now.” (participant 1013, woman not on respiratory therapy)
Proactive vs reactive approach to health	Proactive	“Even though I'm not dealing with it now, it'd be useful to have (treatment) in place when it happens or before it happens…I don't want it to be an emergency when I get to learn it. I Want to try to be on top of it.” (participant 1002, man not on respiratory therapy)
		“I worry about (symptom progression) a lot… If you wait 3 mo, I don't go back till (mo) to see speech, I'm afraid by then I won't have a voice.” (participant 1008, woman not on respiratory therapy)
	Reactive	“In the past I was in the (proactive) group. Yeah. I always would be proactive, like, researching things, asking questions of other people. But now with this diagnosis I put the brakes on that a little bit. There's only so much I can take at once.”—(participant 1023, woman not on respiratory therapy)
		Interviewer: “…do you have any particular goals for how you want to manage your breathing through the process, especially if your breathing becomes affected?”
		Participant: “No, to be honest with you, because I don't know what it's going to be… I don't know what to prepare for until it happens.”—(participant 1007, man not on respiratory therapy)
Likelihood of starting a respiratory treatment	Hesitant	“Well, I will research what it is and if they recommend it makes sense. I would do it. I'm not 1 to just do something because the doctor tells you to.” (participant 1015, woman on NIV)
		“I would have to do more research… I am very active. I've not had anything that's debilitating to me yet, not going on. So, I know that there are things that could be coming down the line. And then when we get to those times, that's when I will have to make a decision. But right now, I don't have to, so I'm not making them.” (participant 1021, woman not on respiratory therapy)
	Open	“I will say probably as soon as possible. Even though I'm not dealing with it now, it'd be useful to have in place when it happens or before it happens.” (participant 1002, man not on respiratory therapy)
Response to description of lung volume recruitment	Hesitant	“…When I need it, I'm going to definitely use it, but it's coming out of sight, out of mind” (participant 1016, man who identified as reactive with his health)
	Open	“I'm definitely up for it” (participant 1002, man)
		“it's a piece of cake” (participant 1006, man)
		“I would need to understand how this is going to benefit me…why should I spend time and I have limited time left…it needs to have a tangible benefit” (participant 1004, woman)
		“If that's what's recommended. I'm going to try whatever is recommended” (participant 1008, woman who identified as proactive with her health)
Response to description of NIV	Hesitant	“Might just be getting used to sleeping with something on my face at night.” (participant 1017, man not on respiratory therapy)
		“I have concerns about making it feel claustrophobic. And that would make it harder for me to breathe having a device.” (participant 1020, woman not on respiratory therapy)
		“I wouldn't be real crazy about it…The thing over your head and the hose and all that stuff to me I'd rather avoid that if I could but if it's keeping me alive I'd do it.” (participant 1012, man who identified as being proactive with his health)
		“I don't really like wearing a mask when I'm sleeping…you have this machine and it requires maintenance and all that other stuff. I would look at that too. What's the time required? Because I've heard from people with CPAP machines that (they) are pain.” (participant 1014, man who identified as being proactive with his health)
	Open	“Initial thoughts is I don't think I would turn that 1 down, because it's used for a method of assistance and not dependency. So, I would consider that quicker than I would consider or not consider a trach.” (participant 1021, woman)
Experience thus far with respiratory care	Discomfort with mask or NIV settings	“…my mouth comes open, I breathe through my mouth. It becomes dry as a bone and that wakes me up and unable to sleep” (participant 1004, woman on NIV)
		“He does it more during the d, because when he lays down with it on, like I said, he's not comfortable and he just won't sleep…He doesn't think it's doing anything… but he just got to push through it and keep trying…” (Caregiver, participant 1005, man on NIV)
		“It's very hard for me to use it to sleep, every night. It's so interruptive… I have a hard time using it at night. Or if I do, I use it like a few hours and then when I get out to go to the bathroom I sometimes just shut it off” (participant 1015, woman on NIV)
		“I did have problems at the very beginning because of I guess the type of mask that they gave me originally…When I got home and I tried it, it was just too much pressure. It was blowing and then when I took it back or I went back, I used the best part, I took that and they said, oh, well, all men breathe through their mouth, not their nose.” (participant 1018, man on NIV)
		“I think that it keeps getting worse where he could end up on a ventilator and things like that, so that's why I try to keep nagging him to use the breathing machine, because (doctor) said that the sooner that he gets on it and uses it, the better he'll be.” (Caregiver, participant 1005, man on NIV)
	Lack of understanding about NIV	“So some kind of breathing, even a video. Um, I guess I could have looked on YouTube and I would probably have found something, but basically, they just wanted to make sure I knew how to use it.” (participant 1004, woman on NIV)
		“Because they said there's negative gasses or something, that the breathing machine is supposed to help…He doesn't understand the machine that he's on now…He doesn't like it” (Caregiver, participant 1005, man on NIV)
	Financial barriers	“just the BiPAP, it was $3,500. And then I had to buy all the mask itself. And that was another $500…I have very high bills where its like $7,900 which I have had now” (Participant 1015, woman on NIV)
Learning style preferences	More than one learning style	“I would definitely want to read an article about what it's supposed to do. Maybe there's a Youtube video of a person actually using it. And then it would be nice to read some reviews about what it is that—whether it serves its intended purpose.” (Participant 1025, man not on respiratory therapy)
Presence and perceived burden of caregivers	Presence of caregiver	“Anything I need or whatever, (my husband)'s always there. Always helpful” (Participant 1015, woman on NIV)
	Absence of caregiver	“I'm a single person and I worry about the care. I do have family, but they live (remotely)…the ALS support groups are not good…” (Participant 1014, man not on respiratory therapy)
		“I can get friends, but they're not medically trained…you can't depend on them as frequently as you would like because they have their own life.” (Participant 1014, man not on respiratory therapy)

Abbreviation: NIV = noninvasive ventilation.

Refusal of Breathing Treatments

Fourteen participants did not use any form of breathing treatment. Of the 10 participants on any respiratory therapies, 2 participants, both women, reported using only breathing exercises. Two individuals reported a previous discussion with their physician about initiating NIV but refused because they felt that the treatments were not needed yet based on their symptoms (Table 2).

Proactive vs Reactive Approach to Health

Throughout the interview process, we noticed that participants' answers referenced whether they felt comfortable conceptualizing a future state of their disease. We asked 14 participants how they tend to manage their health, such as (1) seeking to have as much information as possible early on in disease to help prepare for problems down the road (a “proactive” group) or (2) preferring to have information given as needed to address problems as they arise (a “reactive” group) (eAppendix 1).

Of the 14 participants, 10 reported being proactive, with 4 being men and 6 being women. Of the 10 proactive individuals, 6 reported current breathing symptoms, including 5 participants on respiratory therapies (3 on NIV alone, 1 on NIV + mechanical insufflation-exsufflation, and 1 on NIV + mechanical insufflation-exsufflation + nebulizers).

Proactive individuals approached managing their health in several ways. Some participants reported consuming as much information as possible as an attempt to prepare themselves for future issues. For example, 1 participant remarked, “I want to know everything that's going to happen so that if I start seeing anything I know what to prepare for. I have read so many ALS articles” (Participant 1015, woman on NIV). Others commented that they preferred anticipating future needs by initiating a therapy before the day they need it. One participant reported that their quarterly neurology clinic visits felt too infrequent, as they had a fear that their disease progression would outpace their visit frequency.

In contrast to a proactive approach, other individuals reported that they took a more “reactive” approach to their health. These participants expressed preference to learn about and address problems as they arise.

Of the 4 individuals who reported being reactive toward their health, 3 were men. Half reported current symptoms, and 1 reported using NIV. One woman stated that she is typically proactive but she has approached ALS in a reactive manner.

One participant commented, “I know what the inevitable is going to be. So, I just deal with it…I deal with it as it comes” (Participant 1016). Other participants commented that such an approach encouraged them to be resilient and adaptable to unpredictable changes: “…you have to learn to adapt and move on until something else happens and then learn to deal with that” (Participant 1007, man not on respiratory therapy). When asked about how they would address future issues (e.g., breathing difficulty), participants reported lack of anticipation due to absence of respiratory symptoms.

Likelihood of Starting a Respiratory Treatment

Our initial interview guide asked participants a yes/no prompt regarding whether they would be willing to try a respiratory therapy under the following scenarios:

1. Your doctor recommended it.

2. You had breathing symptoms (such as difficulty lying down, shortness of breath, and interrupted sleep).

3. A test showed that your breathing has weakened.

4. You saw a picture or video of a patient using the therapy.

5. You had an example device in clinic that you could see or even try.

6. You heard from a patient who has used the therapy.

The first 10 interviews followed this format, and all 10 patients agreed to 2 scenarios: they would start a breathing treatment (1) if recommended by their doctor or (2) if a test has shown that their breathing has weakened. Four participants reported that hearing from another patient or seeing a video would not influence their choice on whether to start a treatment.

For the subsequent 14 interviews, we asked participants to rate on a Likert scale from 1 (very unlikely) to 5 (very likely) on their likelihood of starting a respiratory treatment (such as LVR or NIV) (Table 3). The scenarios presented included the following: (1) doctor recommended the treatment; (2) presence of breathing symptoms (such as difficulty lying down, shortness of breath, or interrupted sleep); (3) a test result that showed weakened breathing; (4) viewing a picture or video of a patient using the therapy; (5) access to an example device in clinic that the participant could try; or (6) heard a testimonial from a patient who has used the therapy. At this point in the interview, participants had already received a description of both LVR and NIV.

Table 3.

Likelihood of Agreeing to Start a New Respiratory Treatment by Method of Introduction

Option	Average scorea (n = 14)
Doctor's recommendation	4.58 ± 0.8
Abnormal breathing test	4.18 ± 1.1
Presence of breathing symptoms	4.00 ± 1.2
Example device in clinic	3.82 ± 1.5
Patient testimonial	3.60 ± 1.6
Picture/video of another patient using treatment	2.70 ± 1.6

Scores are reported as mean ± SD.

^aAnswers rated on a Likert scale from 1 (very unlikely) to 5 (very likely).

Four participants, all women currently using NIV, expressed the desire to research a breathing therapy as a supplement to what the physician recommends. A separate group of 4 participants suggested that individuals with ALS should start respiratory therapy as soon as possible. All 4 participants in this latter group reported current breathing symptoms; 2 were women, and 2 were already using NIV.

Response to Descriptions of Respiratory Treatments

LVR

We prompted participants by describing and showing pictures of the use of LVR with a manual resuscitation bag (eAppendix 1). After describing LVR, we asked participants their thoughts on starting such a therapy.

Despite many participants responding favorably, responses appeared to differ by gender, as men tended to have more positive and confident responses, such as, “I’m definitely up for it” (participant 1002, man), and “it’s a piece of cake” (Participant 1006, man). Women, on the other hand, seemed analytical and hesitant, for example: “I would need to understand how this is going to benefit me…why should I spend time and I have limited time left…it needs to have a tangible benefit” (Participant 1004, woman).

In addition, openness to LVR tended to coincide with whether an individual reported that they were “proactive” or “reactive” with approaching their health. Individuals who identified as proactive tended to be more welcoming: “if that's what's recommended. I'm going to try whatever is recommended” (participant 1008, woman who identified as proactive with her health). Whereas reactive participants tended to be more hesitant, such as: “…when I need it, I'm going to definitely use it, but it's coming out of sight, out of mind” (Participant 1016, man who identified as reactive with his health).

NIV

Fourteen participants were also prompted with a description of NIV (referred to as “Bi-PAP” or “home ventilator” in the interview guide) while showing pictures of individuals sleeping with a NIV mask in place (eAppendix 1). Eight individuals were already on NIV at the time of the interview, and 4 of them were woman.

Overall, responses to NIV were more hesitant than those to LVR. Participants expressed concerns about the NIV mask, particularly regarding comfort while sleeping and claustrophobia. Two participants, both of whom lacked breathing symptoms or current respiratory therapies, remarked that they would refuse to use NIV based on lack of perceived benefit. Two individuals who reported they were “proactive” expressed hesitancy toward starting NIV. Some responses to NIV regarded concerns about whether they would become dependent on the device.

Concerns for both treatments centered around understanding the evidence for benefit. Regarding NIV, hesitation seemed to focus on the NIV mask, ability to sleep while wearing it, claustrophobia, lack of understanding of benefit, and whether the machine will induce dependency.

Experience Thus Far With Respiratory Care

Eight participants in our cohort were currently using NIV. Six of the 8 participants reported an initially negative experience with NIV that conveyed frustration, fear, and discomfort. Some participants found the machine settings so uncomfortable that they reported physical and mental discomfort. Several participants reported discomfort with the NIV mask.

In response to initial discomfort on the device, participants may have been under the impression that they have to acclimate to the current device settings rather than have the settings adjusted to their comfort: “…just got to push through it and keep trying” (Participant 1005, man on NIV).

Other barriers to successful NIV use included patient misunderstanding of the device, insurance and financial considerations, and potential disagreement between patient and caregiver over ideal use of NIV.

Learning Style Preferences

We asked participants their preferred learning method for new breathing therapies. There was wide variability across the cohort, and often, participants reported more than 1 learning style. The most commonly endorsed learning methods included kinesthetic (tactile touch, “hands-on”) (n = 12) and reading (n = 11). Less commonly endorsed learning methods included visual (n = 9) and listening (n = 6). Three participants expressed having no preference regarding learning style. Eleven participants expressed interest in more than 1 learning style.

Presence and Perceived Burden of Caregivers

We noticed a contrast in response to respiratory care based on the current presence of a caregiver at home. Most participants cited a partner as their main source of support. Those who currently had a caregiver reported little concern about ability to perform respiratory care therapies at home, citing a strong support structure.

Not all patients reported a strong support system at home. One participant indicated hesitancy with ability to do respiratory care at home, reporting a lack of family but also a distrust in the local ALS support system. The participant also indicated hesitancy to ask friends for help because of lack of medical training or a desire to avoid burdening them.

Implementation Strategies Consistent With Patient Perspectives on ALS Respiratory Therapies

The themes evident in participants' comments map to several concepts in the COM-B and Theoretical Domains Framework. As given in eTable 2, several concepts and corresponding implementation strategies from the Behaviour Change Wheel could be used to promote the uptake of respiratory care interventions in early ALS. Suggested strategies include the following: (1) assessing patient readiness for adopting further information; (2) discussing respiratory therapy options early; (3) providing education across a variety of formats; (4) early identification of barriers to implementing respiratory care in the patient's home; and (5) revisiting NIV adherence and comfort frequently after NIV initiation.

Discussion

In this study, we described the perspectives of patients with ALS regarding respiratory care. These perspectives seemed to differ by self-described approach to managing symptoms. Some individuals preferred a more proactive approach to managing their disease and emphasized advanced planning while others preferred to address issues as they arose. Receptivity to LVR seemed to vary across sex, as men seemed to be more open to LVR than women. The reason for this is unknown, and gender differences regarding respiratory care should be explored in future studies.

We found that participants tended to prefer a variety of learning styles, suggesting that it would behoove an ALS clinic to use multiple learning methods when introducing respiratory therapies. Future work should investigate the effect of providing a respiratory care education package that allows patients to choose their preferred educational resources.

The contrasting “proactive” vs “reactive” approaches to care for ALS may have profound effects on willingness to initiate therapies such as NIV or LVR. Counseling on timing of respiratory care should consider whether a person identifies as “proactive” vs “reactive” to align interests during shared decision-making conversations. Future studies should investigate whether individuals may convert from reactive to proactive or vice versa at different stages of disease.

We found that the most influential factor for initiating respiratory care was a doctor's recommendation to start a treatment. Two other highly rated factors included (1) an objectively abnormal breathing test and (2) the subjective feeling of breathing symptoms. These data suggest that physicians should help patients to make an informed decision about respiratory treatments by pairing their recommendation with a discussion about the patient's current respiratory symptoms as well as interpreting the patients' current respiratory testing results. If the patient's current clinical status warrants NIV, focusing on testing results and symptoms may be far more effective than a patient testimonial or showing a picture/video of someone else using a therapy.

Our results also suggested that an early discussion about respiratory care may be helpful for priming a patient's readiness to initiate therapy. A physician may be hesitant to discuss respiratory care because they assume that a patient is unwilling to discuss it; however, if patients put a high value on physician recommendation, then an early conversation about breathing treatment options may assist subsequent recommendations when the patient's clinical status warrants a more urgent intervention.

Two additional factors likely influencing participant responses include both fear and denial regarding disease progression and the need for respiratory therapies. For example, the severity of these sentiments may strongly influence whether someone is hesitant about respiratory care and/or takes a “reactive” approach to treating ALS. Future studies using semistructured interviews should assess the severity of participant fear and denial to better contextualize drivers behind participant responses to respiratory care discussions.

Few studies have used semistructured interviews to understand how patients with ALS make decisions about respiratory care. A study in 1994 performed interviews of 13 patients with ALS who were currently or imminently using invasive mechanical ventilation.³⁰ Quality of life was the most frequently endorsed factor considered by participants when deciding on invasive mechanical ventilation. A 2010 study performed semistructured interviews at a single center of 9 participants with more advanced ALS than our population (18+ months from diagnosis, mean ALSFRS-R total score 15 ± 7, and 2 participants on invasive ventilation) regarding decision making for assisted ventilation.³¹ In contrast to our study, this 2010 study focused on both invasive ventilation and NIV. Participants perceived invasive ventilation as an “artificial” means for life while NIV was viewed as a “natural” support for breathing. Contrary to our study, most patients with ALS preferred deferring information until it was needed for a decision, whereas our study had relatively fewer participants in the “reactive” group.

Similar to our study, the literature regarding decision making in ALS conveys significant challenges and complexity of discussing interventions relative to the patient's current stage of disease. One study³² performed an online focus group with 105 participants with ALS and suggested creating an early communication agreement that is updated continually as the disease progresses. In a study of 14 participants with ALS, patients' decisions emphasized a focus on the present, rather than anticipating future needs—an approach that may differ from health care clinicians.³³ A review of 27 qualitative studies on decision making in ALS, including 16 studies on mechanical ventilation, found that individuals with motor neuron disease are informed by both disease progression and consideration of the patient values, priorities, and perceived caregiver impact.³⁴

Several participants in our study had discouraging experiences with initiating NIV. Given the known benefits of NIV in ALS, these negative introductions have implications for patients' symptom burden, quality of life, and survival. It would be prudent for ALS programs to identify, anticipate, and develop a structured system for iterative education, introduction, initial setup, and troubleshooting to improve the patient's experience and maximize NIV benefit.

There are several limitations to our study. There is potential for selection bias as we recruited at academic referral centers and the participants may represent a highly motivated subgroup of individuals with ALS with unique demographic and financial backgrounds. We did not stratify enrollment by sex, race, symptom onset site, or center, and so any imbalance in these demographics would limit generalizability. Participant answers may not be generalizable to all stages of disease. We did not screen for underlying behavioral health comorbidities that may affect participant answers. Interviews occurred on a single day at a relatively early stage of disease, so we may have missed the breadth of interparticipant and intraparticipant variation as answers may not be reflective of how values and decisions evolve with disease progression. Because interviews were performed during the COVID-19 pandemic, all conversations were conducted over video teleconference or telephone, rather than in person. The remote interview format may have influenced participant responses. For example, in-person interviews may have elucidated more nonverbal data compared with remote interviewing. However, remote interviews may have helped include patients who might not have been able to make an additional trip to the study centers, thus increasing generalizability.

Further work is necessary to capture the patient perspective regarding respiratory care at all stages of disease. Future studies should identify the significant barriers affecting patients' ability to use home respiratory care and examine how they differ from both clinician and caregiver perceived barriers.³⁵ Hybrid effectiveness-implementation trials could identify the effect of respiratory care strategies on rates of NIV acceptance, patient experience, and quality of life. A further understanding of the patient perspective for respiratory therapy will be critical to enahancing how clinicians can improve respiratory care delivery and overall quality of life for patients with ALS.

TAKE-HOME POINTS

• → Semistructured interviews of persons with amyotrophic lateral sclerosis (ALS) revealed a spectrum of openness to respiratory care discussions.

• → Patients with ALS were most receptive to considering a respiratory intervention based on a physician's recommendation and abnormal pulmonary function test results.

• → Patients with ALS preferred a variety of learning methods for education about respiratory care, highlighting the importance of flexible communication strategies.

• → Participant answers seemed to be influenced by whether they handled their health in a “proactive” (i.e., forward planning) rather than “reactive” (i.e., focusing only on the present) manner.

• → We propose 5 implementation strategies for introducing respiratory interventions to individuals with ALS, which include (1) an early discussion of respiratory care, (2) assessing patient readiness, (3) offering a variety of education formats, (4) identifying a variety of barriers to care, and (5) frequently reassessing tolerance to therapy after initiation.

Author Contributions

J. Ackrivo: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; analysis or interpretation of data. D. Bracy: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; analysis or interpretation of data. L.B. Elman: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. J. Hansen-Flaschen: drafting/revision of the manuscript for content, including medical writing for content. Z. Simmons: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. P. Pasinelli: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. T. Heiman-Patterson: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. S. Kawut: drafting/revision of the manuscript for content, including medical writing for content; study concept or design; analysis or interpretation of data. M.B. Lane-Fall: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; analysis or interpretation of data.

Study Funding

NIH K23 HL-151879, Muscular Dystrophy Association 874016, ALS Association 23-SGP-643 (J. Ackrivo); NIH K24 HL-103844 (S. Kawut); NIH U24 HD113146, NIH R01 HL153735, NIH U01 OD033246, NIH R01 HD105446, NIH R01 HD109229, NIH P30 AI045008, NIH P30 AG059302, NIH R01 HD113618, NIH R01 HL171313, Agency for Healthcare Research and Quality P30HS029745, American Heart Association 962544 (M. Lane-Fall).

Disclosure

J. Ackrivo, D. Bracy, L. Elman, J. Hansen-Flaschen, Z. Simmons, P. Pasinelli, T. Heiman-Patterson, and S. Kawut report no disclosures relevant to the manuscript; M. Lane-Fall reports consultant fees from Janssen and speaker fees from Medtronic. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.