Recognition of online e-cigarette marketing and e-cigarette-related attitudes and behaviors among young adults.

INTRODUCTION: Past research examining the relationship between exposure to online e-cigarette marketing and e-cigarette-related attitudes and behaviors has relied on unaided recall measures that may suffer from self-report bias. To date, few studies have presented participants with e-cigarette marketing stimuli and assessed recognition. This study examined the associations between recognition of online e-cigarette marketing stimuli and e-cigarette-related attitudes and behaviors among young adults in California. METHODS: A non-probability representative sample of young adults (ages 18-24; N=1500) living in California completed an online survey assessing their recognition of online e-cigarette marketing stimuli, including image-based (i.e., Instagram, email) and audiovisual (i.e., YouTube, TikTok) promotions, and positive e-cigarette-related attitudes (e.g., appeal of e-cigarettes) and behaviors (e.g., e-cigarette use). Adjusted and weighted logistic regression analyses were used. RESULTS: 79.0% (n=1185) of young adults, including 78.1% (n=310/397) of participants under 21 years old, recognized online e-cigarette marketing. Participants who reported recognition of stimuli, compared with those who did not, had greater odds of reporting appeal of e-cigarettes (AOR=2.26, 95% CI=1.65-3.09) and e-cigarette purchase intentions (AOR=1.66, 95% CI=1.13-2.43) among all participants, and susceptibility to use e-cigarettes among never users (AOR=2.29, 95% CI=1.59-3.29). CONCLUSIONS: Young adults in California recognized audiovisual and image-based online e-cigarette marketing. Such recognition may lead to positive e-cigarette-related attitudes and behavioral intentions, especially among never users. Future research should examine the causal relationship between the associations found in this study. Findings may inform the development and evaluation of psychometrically valid measures of online e-cigarette marketing exposures. IMPLICATIONS: Recognition of online e-cigarette marketing stimuli was associated with greater odds of reporting appeal and benefits of e-cigarettes, purchase intentions, and lifetime e-cigarette use among all participants, and susceptibility to use e-cigarettes among never users. These findings may motivate the development and evaluation of psychometrically valid measures of online e-cigarette marketing exposures.

Content analysis of email marketing communications among online e-cigarette retailers.

INTRODUCTION: Online e-cigarette retailers use email communications to promote products directly to consumers, which may facilitate e-cigarette use. Little is known about the content of these emails. As such, this study collected emails from online e-cigarette retailers in California to conduct a content analysis. METHODS: This study included 13 online e-cigarette retailers in California using Yelp. To be included in the study, e-cigarette retailers needed a live website, physical retail location (i.e., vape shop), and e-cigarettes available for purchase online. The research team entered each website and signed up (if possible) for an email newsletter. Data were collected from the Gmail Application Programming Interface over a 1-year study period (11/01/21-11/01/22). Members of the research team coded emails for the presence of e-cigarettes, other products, flavors, marketing categories, and promotional activities, among other variables. RESULTS: 749 promotional emails (2.1 avg/per day) were received over the 1-year study period. Second-generation e-cigarettes (n=581, 77.6%) were the most observed product in emails followed by disposable e-cigarettes (n=391, 52.2%). The most common flavor profile was fruit/sweet/liquor (n=424, 56.6%). Emails included links to social media pages (n=366, 48.9%). Online coupons were found in 53.1% (n=398) of the emails. Age warnings were displayed in 8.0% (n=60) of the emails. CONCLUSIONS: E-cigarette retailers' emails promoted new products, flavors, and contained promotional discounts. Future research should examine the impact of exposure to such emails on e-cigarette-related attitudes and behaviors. IMPLICATIONS: Findings from this study may help inform prevention programs and interventions focused on increasing tobacco-related digital media literacy (i.e., evaluate tobacco advertising messages on digital media) among gender and ethnic minorities. Future research should examine if exposure to email marketing is causally linked with e-cigarette use among gender and ethnic minorities.

The effect of discontinuing hypertonic saline or dornase alfa on mucociliary clearance in elexacaftor/tezacaftor/ivacaftor treated people with cystic fibrosis: The SIMPLIFY-MCC Study.

Many people with CF (pwCF) desire a reduction in inhaled treatment burden after initiation of elexacaftor/tezacaftor/ivacaftor. The randomized, open-label SIMPLIFY study showed that discontinuing hypertonic saline (HS) or dornase alfa (DA) was non-inferior to continuation of each treatment with respect to change in lung function over a 6-week period. In this SIMPLIFY substudy, we used gamma scintigraphy to determine whether discontinuation of either HS or DA was associated with deterioration in the rate of in vivo mucociliary clearance (MCC) in participants ≥12 years of age. While no significant differences in MCC endpoints were associated with HS discontinuation, significant improvement in whole and peripheral lung MCC was observed after discontinuing DA. These results suggest that pwCF on ETI with mild lung disease do not experience a subclinical deterioration in MCC that could later impact health outcomes after discontinuing HS, and in fact may benefit from improved MCC after stopping DA treatment.

Examining Tobacco-Related Social Media Research in Government Policy Documents: Systematic Review.

BACKGROUND: Social media data have been used to describe tobacco industry marketing practices, user experiences with tobacco, and youth-oriented protobacco content. OBJECTIVE: Examine the extent to which tobacco-related social media research is cited in government policy documents. SEARCH METHODS: Peer-reviewed tobacco-related social media studies were searched for on Web of Science, PubMed, and other databases from 2004 to 2022. The DOI number for each identified article was then used to search the Overton database to find policy documents citing such research. A secondary, manual search of national and international governmental agency websites was also conducted. SELECTION CRITERIA: Documents were included in this study if they were tobacco-related, written in English, cited social media research in the document text and reference section, and were published by a governmental office or agency. DATA COLLECTION AND ANALYSIS: The analytic sample consisted of (n = 38) government policy documents, and were coded for content themes, agency type, document type, and subsequent citations. MAIN RESULTS: When this research was utilized, it was often in the context of highlighting tobacco industry marketing practices, bringing attention to an issue (eg, youth e-cigarette use), and/or describing how social media platforms can be used as a data source to understand tobacco-related attitudes and behaviors. Agencies that often cited this research were the WHO, FDA, and CDC. The document types included research reports, policy recommendations, industry guidance, legal complaints, and practice-based recommendations. CONCLUSIONS: Tobacco-related social media research has been utilized by government agencies in the last decade to guide the policy process. IMPLICATIONS: Tobacco-related social media research has been used in government policy documents to detail tobacco industry marketing and bring attention to youth exposure to protobacco content online. Continued surveillance of social media may be necessary to track the changing tobacco landscape.

Examining the Peer-Reviewed Literature on Tobacco-Related Social Media Data: Scoping Review.

INTRODUCTION: Tobacco researchers have used social media data to examine tobacco industry marketing practices (eg, influencers), and to document user experience with tobacco products. This study summarized the literature that analyzed tobacco-related social media data, including domain, social media platform, tobacco product type, and themes of findings, among other variables. AIMS AND METHODS: PubMed, PsycINFO, Web of Science, and Communication Source were searched between 2004 and 2022. Peer-reviewed articles were included if they were written in English, included at least one tobacco-related term, and one social media-related term, and analyzed a social media post. Two coders screened all-titles and abstracts. The final sample consisted of (n = 255) articles. Studies were coded for domain, social media platform, tobacco product type, data source, type of data, coding and analytic method, and presence of validation procedure, among other variables. RESULTS: A total of 10 504 820 581 tobacco-related social media posts were assessed across 255 studies. User experience (54.1%) and promotion (23.1%) were the most researched domains. Researchers used data from Twitter the most (42.7%). Text (43.1%) was the most common type of data analyzed. Thematic analysis (80.8%) was the most common analytic technique. Themes of findings from content analyses often pertained to the health effects of tobacco use (61.0%) and promotion (44.2%). CONCLUSIONS: Researchers have analyzed billions of tobacco-related social media posts to describe user experience with, and promotions related to, tobacco products like e-cigarettes on platforms like Twitter. Future research may examine tobacco-related social media data from newer platforms like TikTok. IMPLICATIONS: Real-time surveillance of tobacco-related content on social media can keep the tobacco control community abreast of tobacco industry promotional strategies, user experience with tobacco products, and perceived health effects of tobacco use. A framework may be developed to establish best-practices for social media data collection and analysis, including strategies to identify posts from bot accounts and validate methodological approaches used in thematic analysis.

Effect of elexacaftor/tezacaftor/ivacaftor on mucus and mucociliary clearance in cystic fibrosis.

BACKGROUND: The cystic fibrosis transmembrane conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (E/T/I) is highly effective clinically for those with at least one F508del-CFTR allele. The effects of E/T/I on mucociliary clearance (MCC) and sputum properties are unknown. We, therefore, sought to characterize the effects of E/T/I on in vivo MCC and sputum characteristics hypothesized to impact mucus transport. METHODS: Forty-four participants ≥12 years of age were enrolled into this prospective, observational trial prior to initiation of E/T/I and had baseline measurement of MCC and characterization of induced sputum and exhaled breath condensate (EBC) samples. Study procedures were repeated after 1 month of E/T/I treatment. RESULTS: Average age was 27.7 years with baseline forced expiratory volume in 1 second (FEV1) of 78.2 % predicted. 52 % of subjects had previously been treated with a 2-drug CFTR modulator combination. The average whole lung MCC rate measured over 60 min (WLAveClr60) significantly improved from baseline to post-E/T/I (14.8 vs. 22.8 %; p = 0.0002), as did other MCC indices. Sputum% solids also improved (modeled mean 3.4 vs. 2.2 %; p<0.0001), whereas non-significant reductions in sputum macrorheology (G', G") were observed. No meaningful changes in exhaled breath condensate endpoints (sialic acid:urea ratio, pH) were observed. CONCLUSIONS: E/T/I improved the hydration of respiratory secretions (% solids) and markedly accelerated MCC. These data confirm the link between CFTR function, mucus solid content, and MCC and help to define the utility of MCC and mucus-related bioassays in future efforts to restore CFTR function in all people with CF.

Online Purchase Attempts of Flavored E-Cigarettes to Minors in California Before and After Senate Bill 793.

This survey study assesses whether the online purchase attempt completion rate of e-cigarettes changed after passage of California Senate Bill 793.

Spanish-language tobacco-related posts on Twitter: content analysis.

INTRODUCTION: Twitter data has been used to surveil public sentiment about tobacco products, however, most tobacco-related Twitter research has been conducted with English-language posts. There is a gap in the literature on tobacco-related discussions on Twitter in languages other than English. This study summarized tobacco-related discussions in Spanish on Twitter. METHODS: A set of Spanish terms reflecting electronic cigarettes (e.g., cigarillos electrónicos), cigarettes (e.g., "pitillo"), and cigars (e.g., "cigaro") were identified. A content analysis of tweets (n=1,352) drawn from 2021 was performed to examine themes and sentiment. An initial codebook was developed in English then translated to Spanish and then translated back to English by a bilingual (Spanish and English) member of the research team. Two bilingual members of the research team coded the tweets into themes and sentiment. RESULTS: Themes in the tweets included 1) product promotion (n=168, 12.4%), 2) health warnings (n=161, 11.9%), 3) tobacco use (n=136, 10.1%), 4) health benefits of vaping (n=58, 4.3%), 5) cannabis use (n=50, 3.7%), 6) cessation (n=47, 3.5%), 7) addiction (n=33, 2.4%), 8) policy (n=27, 2.0%), and 9) polysubstance use (n=12, 0.9%). Neutral (n=955, 70.6%) was the most common category of sentiment observed in the data. CONCLUSIONS: Tobacco products are discussed in multiple languages on Twitter and can be summarized by bilingual research teams. Future research should determine if Spanish-speaking individuals are frequently exposed to pro-tobacco content on social media and if such exposure increases susceptibility to use tobacco among never users or sustained use among current users. IMPLICATIONS: Spanish-language pro-tobacco content exists on Twitter, which has implications for Spanish-speaking individuals who may be exposed to this content. Spanish-language pro-tobacco-related posts may help normalize tobacco use among Spanish-speaking populations. As a result, anti-tobacco tweets in Spanish may be necessary to counter areas of the online environment that can be considered pro-tobacco.

Alterations in lipids after initiation of highly effective modulators in people with cystic fibrosis.

Risk of cardiovascular disease (CVD) may be changing in people with cystic fibrosis (pwCF) with widespread use of highly effective modulator therapy (HEMT). We performed a retrospective analysis of patients who had lipids checked before and after initiation of ivacaftor or elexacaftor/tezacaftor/ivacaftor. We hypothesized that HEMT negatively impacts lipids (total cholesterol [TC], low-density lipoprotein [LDL], high-density lipoprotein [HDL], TC/HDL ratio). 41 adult patients were included. Paired t-tests showed statistically significant increases in TC (mean difference 16.3 mg/dL, p = 0.007, n = 40), LDL (mean difference 17.1 mg/dL, p < 0.001, n = 35), and TC/HDL ratio (mean difference 0.40, p = 0.014, n = 39) after HEMT initiation. HDL was unchanged (mean difference -1.5 mg/dL, p = 0.69, n = 39). Linear mixed models showed CF liver disease was associated with significantly blunted changes in TC and LDL. Family history of CVD risk factors was associated with significantly accentuated increases in TC and LDL. These data suggest a role for more lipid screening in pwCF.

Advancing the pipeline of cystic fibrosis clinical trials: a new roadmap with a global trial network perspective.

The growing use of modulator therapies aimed at restoring cystic fibrosis transmembrane conductance regulator (CFTR) protein function in people with cystic fibrosis has fundamentally altered clinical trial strategies needed to advance new therapeutics across an orphan disease population that is now divided by CFTR modulator eligibility. The development of a robust pipeline of nucleic acid-based therapies (NABTs)-initially directed towards the estimated 10% of the cystic fibrosis population who are genetically ineligible for, or intolerant of, CFTR modulators-is dependent on the optimisation of restricted trial participant resources across multiple development programmes, a challenge that will preclude the use of gold standard placebo-controlled trials. Advancement of a full pipeline of symptomatic therapies across the entire cystic fibrosis population will be challenged by smaller effect sizes and uncertainty regarding their clinical importance in a growing modulator-treated population with more mild and stable pulmonary disease. In this Series paper, we aim to lay the foundation for clinical trial strategy and community partnership that must deviate from established and familiar precedent to advance the future pipeline of cystic fibrosis therapeutics.

Monitoring website marketing among leading e-cigarette brands and vendors in California: content analysis.

BACKGROUND: Electronic cigarette (e-cigarette) brands and vendors use websites to promote pro-tobacco messages that may increase susceptibility to use e-cigarettes among never users or help sustain continued e-cigarette use among current users. E-cigarette website marketing is lightly regulated, and little is known about promotional strategies used on e-cigarette companies' websites. This study conducted a content analysis of website marketing from leading e-cigarette companies selling products in California. METHODS: This study identified 20 e-cigarette vendors and 6 e-cigarette brands that had products available for purchase online in California. Two coders visited 26 websites between 06 February 2022 and 17 April 2022. Websites were coded for marketing themes, promotional and interactive content, availability of flavoured e-cigarette products, presence of health warnings, and reference to tobacco control policies. RESULTS: Marketing themes related to physical health benefits of e-cigarette use were found on 50.0% of the websites. 57.7% of the websites had sales/discounts/coupons. 65.4% of the websites had fruit-flavoured disposable e-cigarettes, while 73.1% of the websites had fruit-flavoured e-liquids available for purchase. 69.2% of the websites allowed users to sign up for email newsletters, and 88.9% of such websites did not require users to create an age-verified account to receive email newsletters. CONCLUSIONS: Findings from this study can be used to inform statewide regulations of promotional communications found on e-cigarette companies' websites and encourage enforcement of age-verification procedures. This may help reduce susceptibility to use, or continued use of, e-cigarette products among price-sensitive populations, such as adolescents and young adults.

A thematic analysis of Puff Bar-related content on TikTok.

Background: Puff Bar has rapidly captured a large proportion of the disposable e-cigarette market. To stay abreast of the rapidly changing e-cigarette-product landscape, researchers have turned to social media platforms to monitor e-cigarette-related discussions and marketing trends. TikTok is the latest social media platform to capture the attention of adolescents and young adults; however, e-cigarette-related research using TikTok is limited. Objectives: This study examined Puff Bar-related posts on TikTok to identify themes and user engagement. Methods: Data were collected by scraping publicly available TikTok posts that contained the hashtag #puffplus, between January 31, 2020 and May 4, 2021 (n = 581). The research team used an inductive approach to identify 19 themes from the data. User engagement with posts including the number of likes, shares, plays, and comments was also collected. Results: The most prevalent themes included Music at 75.39% (438/581), followed by Flavors at 51.64% (300/581), Youth/Young Adults at 42.86% (249/581), Tobacco Use at 41.14% (239/581), Nicotine Concentration at 35.11% (204/581), Humor at 19.45% (113/581) and Product Review at 19.1% (111/581). Cessation 1.38% (8/581) and Health Warnings 2.58% (15/581) were two themes rarely observed but commonly engaged with by TikTok users. Conclusions: Health communication strategists should prepare to address TikTok's popularity to combat its contribution to the online e-cigarette environment. Future research should determine the impact of exposure to Puff Bar-related content on TikTok on adolescents' and young adults' attitudes and behaviors.

Feasibility of free-breathing 19 F MRI image acquisition to characterize ventilation defects in CF and healthy volunteers at wash-in.

PURPOSE: To explore the feasibility of measuring ventilation defect percentage (VDP) using 19 F MRI during free-breathing wash-in of fluorinated gas mixture with postacquisition denoising and to compare these results with those obtained through traditional Cartesian breath-hold acquisitions. METHODS: Eight adults with cystic fibrosis and 5 healthy volunteers completed a single MR session on a Siemens 3T Prisma. 1 H Ultrashort-TE MRI sequences were used for registration and masking, and ventilation images with 19 F MRI were obtained while the subjects breathed a normoxic mixture of 79% perfluoropropane and 21% oxygen (O2 ). 19 F MRI was performed during breath holds and while free breathing with one overlapping spiral scan at breath hold for VDP value comparison. The 19 F spiral data were denoised using a low-rank matrix recovery approach. RESULTS: VDP measured using 19 F VIBE and 19 F spiral images were highly correlated (r = 0.84) at 10 wash-in breaths. Second-breath VDPs were also highly correlated (r = 0.88). Denoising greatly increased SNR (pre-denoising spiral SNR, 2.46 ± 0.21; post-denoising spiral SNR, 33.91 ± 6.12; and breath-hold SNR, 17.52 ± 2.08). CONCLUSION: Free-breathing 19 F lung MRI VDP analysis was feasible and highly correlated with breath-hold measurements. Free-breathing methods are expected to increase patient comfort and extend ventilation MRI use to patients who are unable to perform breath holds, including younger subjects and those with more severe lung disease.

The Need for Tobacco-Related Interventions to Incorporate Digital Media Literacy.

This Viewpoint discusses the need for health promotion programs and interventions to bolster tobacco-related digital media literacy among adolescents, young adults, parents, teachers, and public health organizations.

Monitoring the Official YouTube Channels of E-Cigarette Companies: A Thematic Analysis.

BACKGROUND: E-cigarette companies use YouTube to foster brand awareness, market their products, and interact with current and future tobacco users. However, research on the official YouTube channels of e-cigarette companies is limited. This study determined the themes of, and degree of user engagement with, videos posted to the official channels of e-cigarette companies on YouTube. METHODS: Data were collected from the official YouTube channels of seven e-cigarette companies by scraping (i.e., electronically copying) the videos. The earliest video was posted on October 10, 2013, and the most recent video was posted on April 22, 2021 (n = 260). An inductive approach was used to identify themes in the data. User engagement with posts including number of likes, dislikes, and comments were also collected. RESULTS: Prevalent themes included branding (n = 250 of 260 videos, 96%), youth use (n = 222, 85%), and tobacco use (n = 210, 81%), while less common themes included misleading health statements (n = 4, 2%), personal choice (n = 4, 2%), and antitobacco (n = 2, 1%). Videos that contained the themes testimonial, product design features, and instructional received the highest mean number of likes. Videos that contained the themes antitobacco, cessation, and testimonial received the highest mean number of dislikes. The 260 videos in this study were collectively viewed 6,619,700 times as of May 5, 2021. CONCLUSIONS: Videos from the official YouTube channels of seven e-cigarette companies often focused on branding and user experience but rarely mentioned cessation. While videos about cessation were rare, they received the second highest mean number of dislikes. Future research should assess the impact of exposure to e-cigarette-related content on YouTube and e-cigarette-related attitudes and behaviors.

An Analysis of Twitter Posts About the U.S. Food and Drug Administration's Menthol Ban.

INTRODUCTION: Although the U.S. Food and Drug Administration (FDA) banned characterizing flavors in cigarettes in 2009, this initial ban exempted menthol. After examining numerous reports on the adverse health effects of menthol cigarettes, the FDA proposed a menthol ban in April 2022. This study analyzed Twitter data to describe public reaction to this announcement. AIMS AND METHODS: Posts containing the word "menthol" and/or "#menthol" were collected from April 21, 2022 to May 5, 2022 from Twitter's Streaming Application Programming Interface (API). A random sampling procedure supplied 1041 tweets for analysis. Following an inductive approach to content analysis, posts were classified into one or more of 11 themes. RESULTS: Posts discussed the FDA announcement (n = 153, 14.7%), racial discrimination (n = 101, 9.7%), distrust in government (n = 67, 6.4%), inconsistencies between policies (n = 52, 5.0%), public health benefits (n = 42, 4%), freedom of choice (n = 22, 2.1%), and health equity (n = 21, 2.0%). Posts contained misinformation (n = 20, 1.9%), and discussed the potential for illicit markets (n = 18, 1.7%) and the need for cessation support (n = 4, 0.4%). 541 (52.0%) tweets did not fit into any of the prescribed themes. CONCLUSIONS: Twitter posts with the word "menthol" commonly discussed distrust in government and mentioned racial discrimination. Findings demonstrated the possibility of near real-time Twitter monitoring of public opinion on a menthol ban. These data may be valuable for designing tobacco control health communication campaigns in the future. IMPLICATIONS: The U.S. FDA proposed a ban on menthol cigarettes in April 2022. This study's content analyzed Twitter posts over a 2-week period to understand the public's response to the proposed menthol ban. Twitter posts with the word "menthol" often discussed distrust in government and mentioned racial discrimination. Findings demonstrated the possibility of near real-time Twitter monitoring of public opinion of regulatory action. Findings underscore the need to educate the public about the potential health benefits of banning menthol from cigarettes, particularly for populations that experience tobacco-related health disparities.

Elexacaftor/tezacaftor/ivacaftor and gastrointestinal outcomes in cystic fibrosis: Report of promise-GI.

BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI) improves pulmonary disease in people with cystic fibrosis (PwCF), but its effect on gastrointestinal symptoms, which also affect quality of life, is not clear. METHODS: PROMISE is a 56-center prospective, observational study of ETI in PwCF >12 years and at least one F508del allele. Gastrointestinal symptoms, evaluated by validated questionnaires: Patient Assessment of Upper Gastrointestinal Disorders-Symptom (PAGI-SYM), Patient Assessment of Constipation-Symptom (PAC-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL)), fecal calprotectin, steatocrit and elastase-1 were measured before and 6 months after ETI initiation. Mean difference and 95% confidence intervals were obtained from linear regression with adjustment for age and sex. RESULTS: 438 participants fully completed at least 1 questionnaire. Mean (SD) for baseline PAGI-SYM, PAC-SYM, and PAC-QOL total scores were 0.56 (0.59), 0.47 (0.45), and 0.69 (0.53) out of maximum 5, 4, and 5, respectively (higher score indicates greater severity). Corresponding age- and sex-adjusted 6 months mean changes (95% CI) in total scores were -0.15 (-0.21, -0.09) for PAGI-SYM, -0.14 (-0.19, -0.09) for PAC-SYM, and -0.15 (-0.21, -0.10) for PAC-QOL. While statistically significant, changes were small and unlikely to be of clinical importance. Fecal calprotectin showed a change (95% CI) from baseline of -66.2 µg/g (-86.1, -46.2) at 6 months, while fecal elastase and steatocrit did not meaningfully change. CONCLUSIONS: After 6 months of ETI, fecal markers of inflammation decreased. Gastrointestinal symptoms improved, but the effect size was small. Pancreatic insufficiency did not improve.

Discontinuation versus continuation of hypertonic saline or dornase alfa in modulator treated people with cystic fibrosis (SIMPLIFY): results from two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials.

BACKGROUND: Reducing treatment burden is a priority for people with cystic fibrosis, whose health has benefited from using new modulators that substantially increase CFTR protein function. The SIMPLIFY study aimed to assess the effects of discontinuing nebulised hypertonic saline or dornase alfa in individuals using the CFTR modulator elexacaftor plus tezacaftor plus ivacaftor (ETI). METHODS: The SIMPLIFY study included two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials at 80 participating clinics across the USA in the Cystic Fibrosis Therapeutics Development Network. We included individuals with cystic fibrosis aged 12-17 years with percent predicted FEV1 (ppFEV1) of 70% or more, or those aged 18 years or older with ppFEV1 of 60% or more, if they had been taking ETI and either (or both) mucoactive therapies (≥3% hypertonic saline or dornase alfa) for at least 90 days before screening. Participants on both hypertonic saline and dornase alfa were randomly assigned to one of the two trials, and those on a single therapy were assigned to the applicable trial. All participants were then randomly assigned 1:1 to continue or discontinue therapy for 6 weeks using permuted blocks of varying size, stratified by baseline ppFEV1 (week 0; ≥90% or <90%), single or concurrent use of hypertonic saline and dornase alfa, previous SIMPLIFY study participation (yes or no), and age (≥18 or <18 years). For participants randomly assigned to continue their therapy during a given trial, this therapy was instructed to be taken at least once daily according to each participant's pre-existing, clinically prescribed regimen. Hypertonic saline concentration was required to be at least 3%. The primary objective for each trial was to determine whether discontinuing was non-inferior to continuing, measured by the 6-week change in ppFEV1 in the per-protocol population. We established a non-inferiority margin of -3% for the difference between groups in the 6-week change in ppFEV1. Safety outcomes were analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT04378153. FINDINGS: From Aug 25, 2020, to May 25, 2022, a total of 672 unique participants were screened for eligibility for one or both trials, resulting in 847 total random assignments across both trials with 594 unique participants. 370 participants were randomly assigned in the hypertonic saline trial and 477 in the dornase alfa trial. Participants across both trials had an average ppFEV1 of 96·9%. Discontinuing treatment was non-inferior to continuing treatment with respect to the absolute 6-week change in ppFEV1 in both the hypertonic saline trial (-0·19% [95% CI -0·85 to 0·48] in the discontinuation group [n=133] vs 0·14% [-0·51 to 0·78] in the continuation group [n=140]; between-group difference -0·32% [-1·25 to 0·60]) and dornase alfa trial (0·18% [-0·38 to 0·74] in the discontinuation group [n=199] vs -0·16% [-0·73 to 0·41] in the continuation group [n=193]; between-group difference 0·35% [-0·45 to 1·14]), with consistent results in the intention-to-treat populations. In the hypertonic saline trial, 64 (35%) of 184 in the discontinuation group versus 44 (24%) of 186 participants in the continuation group and, in the dornase alfa trial, 89 (37%) of 240 in the discontinuation group versus 55 (23%) of 237 in the continuation group had at least one adverse event. INTERPRETATION: In individuals with cystic fibrosis on ETI with relatively well preserved pulmonary function, discontinuing daily hypertonic saline or dornase alfa for 6 weeks did not result in clinically meaningful differences in pulmonary function when compared with continuing treatment.