Badenes‑Bonet et al. BMC Pulmonary Medicine (2022) 22:340 https://doi.org/10.1186/s12890‑022‑02134‑4 RESEARCH Predictors and changes of physical activity in idiopathic pulmonary fibrosis Diana Badenes‑Bonet1,2,4, Anna Rodó‑Pin1, Diego Castillo‑Villegas5, Vanesa Vicens‑Zygmunt6, Guadalupe Bermudo6, Fernanda Hernández‑González7, Karina Portillo8, Juana Martínez‑Llorens1,2,3,4, Roberto Chalela1,2,4, Oswaldo Caguana1, Jacobo Sellarés7, Maria Molina‑Molina3,6, Xavier Duran9, Joaquim Gea1,2,3,4, Diego Agustín Rodríguez‑Chiaradia1,2,3,4 and Eva Balcells1,2,3,4* Abstract Background: Different clinical predictors of physical activity (PA) have been described in idiopathic pulmonary fibro‑ sis (IPF), but studies are lacking evaluating the potential role of muscle strength and anxiety and depression symp‑ toms in PA limitation. Moreover, little is known about the impact of changes in PA in the course of the disease. The aim of the present study was to investigate the relationship between baseline PA and a wide range of variables in IPF, to assess its longitudinal changes at 12 months and its impact on progression free‑survival. Methods: PA was assessed by accelerometer and physiological, clinical, psychological factors and health‑related quality of life were evaluated in subjects with IPF at baseline and at 12 month follow‑up. Predictors of PA were determined at baseline, evolution of PA parameters was described and the prognostic role of PA evolution was also established. Results: Forty participants with IPF were included and 22 completed the follow‑up. At baseline, subjects performed 5765 (3442) daily steps and spent 64 (44) minutes/day in moderate to vigorous PA. Multivariate regression models showed that at baseline, a lower six‑minute walked distance, lower quadriceps strength (QMVC), and a higher depres‑ sion score in the Hospital Anxiety and Depression scale were associated to lower daily step number. In addition, being in (Gender‑Age‑Physiology) GAP III stage, having a BMI ≥ 25 kg/m2 and lower QMVC or maximum inspiratory pressure were factors associated with sedentary behaviour. Adjusted for age, gender and forced vital capacity (FVC) (%pred.) a lower progression‑free survival was evidenced in those subjects that decreased PA compared to those that main‑ tained, or even increased it, at 12 months [HR 12.1 (95% CI, 1.9–78.8); p = 0.009]. Conclusion: Among a wide range of variables, muscle strength and depression symptoms have a predominant role in PA in IPF patients. Daily PA behaviour and its evolution should be considered in IPF clinical assessment and as a potential complementary indicator of disease prognosis. Keywords: Physical activity, Idiopathic pulmonary fibrosis, Predictors, Muscle strength, Depression, Prognosis © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Introduction Idiopathic pulmonary fibrosis (IPF) is a progressive fibro- sing interstitial lung disease (ILD) with a high morbidity and mortality [1]. Exertional dyspnoea, the predominant symptom in IPF, worsens as disease progresses and leads to exercise limitation and reduced levels of physical activ- ity (PA) [2]. In this respect, objectively measured PA by Open Access *Correspondence: ebalcells@psmar.cat 1 Interstitial Lung Disease Unit, Respiratory Medicine Department, Hospital del Mar, Passeig Marítim 25, 08003 Barcelona, Spain Full list of author information is available at the end of the article Page 2 of 9Badenes‑Bonet et al. BMC Pulmonary Medicine (2022) 22:340 accelerometry is reduced in IPF patients, compared to healthy individuals, not only in advanced IPF but also in earlier stages [3]. Furthermore, in several cross-sectional studies, PA has been associated to different physiological variables [i.e. forced vital capacity (FVC), carbon mon- oxide diffusing capacity (DLCO) and 6-min walked dis- tance (6MWD)], as well as patient-reported outcomes such as dyspnoea, fatigue and quality of life [3–5]. How- ever, other relevant parameters such as muscle strength or psychological factors have not been explored in detail and, information regarding their contribution or impact on PA in IPF patients is under-researched. Additionally, there are few longitudinal studies that have examined changes of PA over time in IPF patients [6, 7]. These studies have observed a significant annual decline in PA and have highlighted that this decline could be disproportionate to changes in classical physiological variables, such as lung function and exercise capacity. Moreover, the effects of PA in mortality or progression in IPF are controversial. Bahmer et al. [6] reported an inde- pendent association between a lower baseline PA (i.e. steps/day) adjusted by age, sex and antifibrotic therapy, and a higher 3 year mortality risk. By contrast, in a more recent study, neither baseline daily step count (DSC) nor its 12 month decline were associated with long-term sur- vival [7]. The primary aims of our study were: (a) to investi- gate the relationship between baseline PA and a wide range of variables, including lung function, exercise capacity, dyspnoea, anxiety and depression symptoms, health-related quality of life (HRQoL) and muscle strength in IPF, and (b) to assess longitudinal changes in their PA over 12  months. The secondary aim was to evaluate the impact of PA changes on progression free-survival. Methods Study population Patients with IPF diagnosis were consecutively recruited from a specialized ILD clinic in five tertiary-teaching hospitals. Exclusion criteria were relevant comorbidi- ties which prevented PA measurement or the six-minute walking test (6MWT) performance, clinical worsening or hospital admission during two months prior to inclusion, severe pulmonary hypertension detected by echocar- diogram [8], treatment with corticosteroid therapy, diagnosis of an active neoplasia or being included in a rehabilitation program. Study design This is a multicentre prospective study divided into two phases (Fig.  1). Firstly, a cross-sectional evaluation was performed including clinical variables collection such as demographic, (Gender-Age-Physiology) GAP index, body mass index (BMI), Charlson comorbidity index and diagnosis and treatment received. Pulmonary function (PFTs), exercise capacity, respiratory and limb muscle strength and body composition were assessed and dysp- noea, anxiety, depression and HRQoL questionnaires were completed. Moreover, PA was assessed with an Fig. 1 Study flowchart. mMRC Modified medical research council; SGRQ St. George respiratory questionnaire; HADS Hospital anxiety and depression scale; PFTs Pulmonary function tests; 6MWT Six‑minute walking test Page 3 of 9Badenes‑Bonet et al. BMC Pulmonary Medicine (2022) 22:340 accelerometer. A follow-up evaluation was performed at 12 months. The study was carried out according to the principles of the Declaration of Helsinki for human investigations and approved by the local Ethics Committee with allocation number 2017/7241/I. All participants signed the appro- priate informed consent prior to their inclusion. Study variables PA measurement Participants were provided with a triaxial accelerometer (SenseWear Pro2 Armband, SWA; Body Media, Pitts- burgh, PA, USA) and were instructed to wear the moni- toring device on their left triceps for 23  h a day, for 7 consecutive days except for the time spent in personal hygiene [9]. The minimum recording time for the analysis was defined as at least 3 days, recording more than 70% of the daytime (8–22 h), excluding the first and last day of the record [10]. Parameters of PA included DSC, daily minutes of moderate-to-vigorous PA (MVPA ≥ 3 metabolic equiva- lents [METS]) and sedentary time (< 1.5 METS) [10, 11]. PA level (PAL: total daily energy divided by sleeping energy expenditure) was also registered and categorized. An inactive person was defined as having a PAL < 1.40, whereas a sedentary person as having a PAL 1.40–1.69, and an active person as having a PAL ≥ 1.70 [12]. Dyspnoea, HRQoL and anxiety and depression The modified Medical Research Council dyspnoea scale (mMRC) [13], the St. George Respiratory Questionnaire (SGRQ) [14] and the Hospital Anxiety and Depression Scale (HADS) [15] were completed as indicated. Lung function and exercise capacity PFTs including forced spirometry (EasyOne, NDD Medi- cal Technologies, Zurich, Switzerland) static pulmonary volumes (body plethysmography), DLCO (MasterLab, Jae- ger, Würzburg, Germany) [16, 17] and the 6MWT were performed according to international guidelines [18]. Arterial blood gas measurement at room air was also per- formed (RapidLab500, Siemens, Erlangen, Germany). Body mass and composition Anthropometric variables including BMI and fat-free mass index (FFMI) (acquired by bioelectrical impedance; BODYSTAT 1500, Bodystat Ltd, Isle of Man, UK) were obtained. Respiratory and peripheral muscle strength Respiratory muscle strength [maximum inspiratory pres- sure (MIP), maximum expiratory pressure (MEP)] both measured at the mouth, as well as peripheral muscle strength (hand grip: JAMAR 030J1, Chicago, IL, USA) and isometric quadriceps maximum voluntary contrac- tion (QMVC: BIOPAC dynamometer, BIOPAC Systems, Schooner, CA, USA) were assessed following previ- ously described methodology [19]. The highest value of three manoeuvres was recorded. Data were expressed as absolute values and using validated reference equations [20–22]. Follow‑up evaluation The study participants were assessed after 12 months by repeating the complete protocol. Progression-free sur- vival was assessed up to 24  months after inclusion, and data were obtained from institutional records. A rela- tive decline of FVC > 10% and/or DLCO > 15% during the 24 month follow-up were considered as disease progres- sion [23, 24]. Statistical analysis Categorical variables were expressed as number and per- centages, whereas continuous variables as mean (stand- ard deviation, SD), or median (25th and 75th percentiles, P25-P75) when normality assumption was not fulfilled. A multivariate linear regression model was built for each PA variable (DSC, time in MVPA and sedentary time). Potential predictors including BMI, FFMI, FVC (%pred.), DLCO (%pred.), 6MWT (distance and SpO2), respiratory and peripheral muscle strength, degree of dyspnoea, SGRQ and HAD score were identified from the literature. Covariates with a p-value < 0.1 were entered in the model, and successively excluded if not associated with the out- come (p < 0.05). Finally, the most parsimonious model that still explained the data was built for each outcome. Longitudinal changes in PA were tested by paired t-test or Wilcoxon signed-rank test as appropriate. Progres- sion free-survival analysis according to PA changes was analysed by the Kaplan–Meier method. Cox proportional hazard models were performed, adjusted for gender, age and FVC (%pred.), for progression or mortality out- comes. A cut-off point of change of DSC was calculated by maximally selected rank statistic and performed with the web-based tool Cutoff Finder [25]. This method takes jointly into account the marker, the event as well as time to event. A p-value < 0.05 was considered as statistically significant. The analysis was performed using the IBM SPSS statistics pack for Windows (Version 23.0, IBM Corp., Armonk, NY, USA). Results Study participants Forty participants with IPF were enrolled from July 2017 to December 2019 (Table 1). Page 4 of 9Badenes‑Bonet et al. BMC Pulmonary Medicine (2022) 22:340 The mean age (SD) at first evaluation was 71.4 (6.5) years, and 75% were males. The mean (SD) FVC % pred. and DLCO % pred. was 79.2 (19.4) % and 44.7  (14.4) %, respectively. Thirty patients (75%) were classified in GAP stages I-II. In the 6MWT, patients walked a mean distance of 451.6  m (92.7%pred.) and showed a mean SpO2 of 90%. Respiratory and peripheral muscle strength were roughly preserved in all subjects. Total mean score in the SGRQ was 30.3 and HAD depression and anxiety score were 6 and 5, respectively. Of the 40 patients studied at baseline, 22 (55%) com- pleted the follow-up. One patient died before study completion, 2 declined and 1 was included in a reha- bilitation program during the follow-up period. The 14 remaining subjects were not included, as the 12 month PA measurement was to be completed during the COVID-19 pandemic, and we considered PA and other clinical data could be biased by the lockdown. Accord- ingly, all PA measurements were performed prior to COVID-19 pandemic to avoid confounders. Baseline PA parameters and their predictors At baseline, subjects performed 5765 (3442) daily steps and spent 64 (44) minutes/day in MVPA. The mean sedentary time was 725 (44) minutes/day. Accord- ing to PAL, 45.9% of the patients were inactive, 43.2% sedentary and 10.8% active. A lower 6MWD, lower QMVC, and a higher depression score were associated to lower DSC. Sedentary behaviour was associated to the presence of GAP III stage, a BMI ≥ 25 kg/m2 and a low QMVC or MIP. A lower time spent in MVPA was related to a lower QMVC or MIP (Table 2). Longitudinal changes in PA There were no significant differences in baseline char- acteristics or PA variables between completers and non-completers except in the anxiety score, which was higher in the non-completer group. DSC decreased by a mean of − 789 (p = 0.054). The increase in sedentary time was of 17.5  min/day (p = 0.073). No statistically significant changes were observed in MVPA [9.1  min/ day; p = 0.256], neither in PAL categories (p = 0.513) (Fig.  2). Regarding changes in other clinical and func- tional variables, only DLCO and SpO2 during the 6MWT had significant changes over 12 months. Table 1 Clinical characteristics of the study population (n = 40) Data are presented as mean (SD) and n (%) unless otherwise specified GAP Gender‑age‑physiology; FVC Forced vital capacity; TLC Total lung capacity; DLCO Carbon monoxide diffusion capacity; PaO2 Arterial oxygen partial pressure; 6MWT Six‑minute walking test; SpO2 Peripheral oxygen saturation; MIP Maximum inspiratory pressure; MEP Maximum expiratory pressure; QMVC Quadriceps maximum voluntary contraction; BMI Body mass index; FFMI Fat‑ free mass index; HRQoL Health‑related quality of life; mMRC Modified medical research council; SGRQ St. George respiratory questionnaire; HAD Hospital Total population (n = 40) Demographic Age (years) 71.4 (6.5) Gender: male 30 (75) Smoking status: current or former smoker 29 (72.5) Working status: active 3 (7.5) GAP index (stage I/II/III), (%) 35/40/25 Diagnosis and treatment Time since diagnosis (months), median (p25– p75) 18.5 (11.2–42.6) Ambulatory oxygen therapy 6 (15) Antifibrotic therapy 30 (75) Charlson comorbidity index, median (p25–p75) 4 (3–6) Lung function‡ FVC (% pred.) 79.2 (19.4) TLC (% pred.) 70.6 (14.6) DLCO (% pred.) 44.7 (14.4) PaO2 (mm Hg) 81.3 (8.7) Exercise capacity (6MWT) Distance (m) 451.6 (92.7) Distance (% pred.) 96.2 (18.6) Basal SpO2 (%) 95.1 (2.4) Mean SpO2 (%) 90.1 (5.8) Minimum SpO2 (%) 87.5 (6.5) ΔSpO2 (%), median (p25–p75) § 7 (4–12.8) Muscular strength MIP (% pred.) 87.6 (26.3) MEP (% pred.) 75.3 (23.7) Non‑dominant hand‑grip (kg) 30.8 (9.3) Non‑dominant hand grip (% pred.) 113.4 (19.7) QMVC (kg) 33.6 (9.9) QMVC (% pred.) 91.9 (25.2) Body mass and composition BMI (kg/m2) 27.4 (4.6) FFMI (kg/m2) 17.8 (2.1) Symptoms, HRQoL and psychological factors Dyspnoea (mMRC 0–4), median (p25–p75) 1 (0.25–2) SGRQ score (0–100) Total 30.3 (20.1) Activity 48.2 (24.2) Symptoms 34.4 (22.4) Impact 27.5 (20.8) HAD scale (0–21) Anxiety 6 (3.6) Depression 5 (4.4) anxiety and depression § ΔSpO2%, percentage of change between baseline and exercise values ‡ TLC (n = 31), DLCO (n = 33), PaO2 (n = 33) Table 1 (continued) Page 5 of 9Badenes‑Bonet et al. BMC Pulmonary Medicine (2022) 22:340 Progression free‑survival analysis Patients who died or progressed had a poor lung function, a higher 6MWT desaturation, higher GAP score at baseline, and a higher DSC decline over 12  months than free-progression survivors (1769 vs. −  28; p = 0.016). The optimal cut-off point of DSC was -895 steps for predicting the 24  month progres- sion-free survival. Kaplan–Meier curves showed that patients who reduced their PA ≥ 895 steps per day had a lower progression-free survival than those who did not [18.4  months (95%CI, 15.6–21.2) vs. 22.5 (95%CI 20.6–24.4); p = 0.004] (Fig.  3). In the Cox regression, a change ≥ to this cut-off point, was associated with a higher progression or mortality risk at 24 months after adjusting for age, sex and FVC (%pred.) [HR 12.1 (95% CI 1.9–78.8); p = 0.009]. Discussion The main findings of the present study are that quadri- ceps strength and psychological factors (depression) were identified as novel independent predictors of PA in IPF patients. Moreover, the DSC decline at 12  months was marked; with the 895 daily step threshold being a good discriminant of free-progression survival. In the present study, PA behaviour was not always con- sistent with previous literature. In this regard, a higher DSC was related to a higher 6MWD, being consistent with previous studies [3, 5, 26]. By contrast, we observed Table 2 Independent predictors of physical activity parameters (daily steps, sedentary time, and time in MVPA) in 40 IPF patients at baseline GAP index was dichotomized to GAP I‑II and GAP III. BMI was dichotomized by BMI < 25 and ≥ 25 Each column is a single multivariate lineal regression model including as covariates the variables that show a coefficient in each column. Degree of dyspnoea, FVC %pred., Total SGRQ score and HAD anxiety score, were tested as potential predictors, and finally not included because they were not independently related to the outcome, nor modified estimates for the remaining variables MVPA Moderate to vigorous physical activity; 6MWD Six‑minute walked distance; QMVC Quadriceps maximum voluntary contraction; HADS Hospital anxiety and depression scale; GAP Gender‑age‑physiology; MIP Maximum inspiratory pressure; BMI Body mass index Variables Steps per day Sedentary time (mins/day) Time in MVPA (mins/day) β (95% CI) p β (95% CI) p (β 95% CI) p GAP: stage III – – − 27.9 (− 52.6, − 3.2) 0.028 – – 6MWD (m) 13.7 (4, 23.5) 0.007 – – – – MIP (%pred.) – – − 0.89 (− 1.3, − 0.47) < 0.001 0.88 (0.47,1.3) < 0.001 QMVC (%pred.) 41.7 (7.2, 76.2) 0.019 − 0.57 (− 1.02, − 0.11) 0.016 0.69 (0.23, 1.14) 0.004 BMI: ≥ 25 (kg/m2) – – 24.5 (0.32, 48.7) 0.047 – – HADS score (depression) − 214.6 (− 416.6, − 12.5) 0.038 – – – – Adjusted R2 0.455 0.561 0.470 Fig. 2 Physical activity parameters at baseline and 12 month follow‑up (n = 22). Bars graph show the mean and standard deviation. PA Physical activity; MVPA Moderate to vigorous physical activity Page 6 of 9Badenes‑Bonet et al. BMC Pulmonary Medicine (2022) 22:340 no association between any PA parameter and lung func- tion, as reported by previous research. A relevant and novel finding of our study was that quadriceps strength was independently associated with the amount and inten- sity of PA, as well as with sedentary time. The relation- ship between peripheral muscle dysfunction and reduced PA, is well-documented in other respiratory disorders, but has never been reported specifically in IPF [27, 28]. In ILD, previous research was focused on the role of quadriceps strength on exercise capacity and not on PA, and has the limitation that included heterogeneous groups of ILD patients [29, 30]. Factors such as ageing, hypoxia, oxidative stress, malnutrition and decondi- tioning due to reduced PA levels, could be associated to potential peripheral muscle dysfunction in IPF, but stud- ies determining its specific causes and pathophysiological mechanisms are lacking [31]. In a similar direction, our results evidenced that a lower MIP was related to a lower time spent in MVPA and a higher sedentary time. It is well established that patients with ILD present a progressive decrease in lung function, lung compliance and an increase in elastic load, secondary to fibrosis. Consequently, the predomi- nant symptom is exertional dyspnoea, which leads to a reduced exercise capacity. Accordingly, several studies have evaluated respiratory muscle strength in ILD, point- ing out that the chest mechanical properties remain sta- ble without relationship with lung volume reduction [32, 33] until advanced stages of the disease. Moreover, recent diaphragmatic ultrasound studies, evidence a reduced mobility and diaphragmatic thickness during deep inspiration in ILD subjects compared with healthy indi- viduals, showing no differences in its strength [34]. Our results are in line with the above-mentioned studies, as we found no clear respiratory muscle impairment in our population, although a mild relationship was identified between MIP and PA intensity. One possible explanation could be PA avoidance, leading to deconditioning and muscle wasting. Moreover, mechanical diaphragmatic restraints, could increase the work of breathing result- ing in a chronic overload, but this would probably have more impact in muscle endurance that in strength. In this regard, this increased load in respiratory muscles, added to rapid shallow breathing, could increase breathless- ness and contribute to reduce PA. In view of the present results, we believe that peripheral and respiratory muscle strength assessment could be of potential interest, and, mainly to direct training strategies to improve exercise tolerance, dyspnoea, and consequently PA. Additionally, our study showed that a higher depression score was independently associated with a lower DSC. In other chronic lung diseases such as COPD, depres- sion symptoms have been prospectively associated with a reduction in PA at 6 month follow-up [35]. Specifically in ILD, a recent longitudinal study evidenced that depres- sive symptoms showed a trend towards significance at predicting reduced baseline DSC when adjusting for age, smoking status and lung function [36]. According to our results, psychological status could have an influence on PA in IPF subjects, and therefore, psychological assess- ment should be considered, to better target areas that can potentially impact on PA levels. The mean decline in DSC after 12 months in our study was relevant and somewhat different from previous observations. To our knowledge, only two previous stud- ies have focused on changes of PA in IPF, and the popula- tion profile, design, and outcomes of each study must be considered when comparing to our data. Prasad et  al. [7] observed a slightly lower decline in DSC after 12  months follow-up in 37 IPF patients. A possible confounder in this study could be the inclusion of lung transplant candidates; and their participation in rehabilitation programs. In addition, Bahmer et  al. [6] reported almost a 50% decline in DSC in 3  years, of 23 survivors of an initial cohort of 46 IPF patients. Surpris- ingly, the annual decline in PA was higher than in our study, despite our patients had similar lung function and a lower baseline PA. Nevertheless, their study provided no information about other PA parameters. Another rele- vant aspect observed in our study was that the PA decline was not accompanied by significant changes in other physiological parameters, such as FVC or 6MWD. This could be partially explained by the short follow-up period and clinical profile of our population (i.e. mild FVC impairment, preserved 6MWD, and a high percentage of patients treated with antifibrotic therapy). Together, our Fig. 3 Kaplan–Meier progression‑free survival curves at 24 months in IPF patients who decline ≥ 895 steps/day and those who do not decline (n = 22). IPF idiopathic pulmonary fibrosis Page 7 of 9Badenes‑Bonet et al. BMC Pulmonary Medicine (2022) 22:340 observations are in line with previous studies that sup- port the idea that the PA decline could be prior to pul- monary function or exercise capacity deterioration, being dependent of other factors as disease progresses, and therefore its longitudinal evaluation could be a comple- mentary tool when evaluating IPF progression [6]. Finally, we evaluated the prognostic value of PA changes over 12  months. To our knowledge, our study is the first to show a threshold for longitudinal changes of DSC (measured by accelerometer) in predicting pro- gression or mortality. There is little and controversial information on the effects of PA in robust outcomes in IPF, and it focuses mainly on baseline assessment of PA. Bahmer et  al. [6] reported an independent associa- tion between a lower baseline DSC (adjusted by age, sex and antifibrotic therapy) and a higher risk of mortality at 3 years. Moreover, Shingai et al. [37] demonstrated that DSC was a good predictor of 1 year mortality in 87 IPF patients at the time of diagnosis and, additionally they first established a cut-off point (3473 steps) for predicting mortality. By contrast, Prasad et al. [7] observed no asso- ciation between baseline daily steps count or its decline over 12 months with better long-term survival. Some limitations of our study should be mentioned. Firstly, the relatively small sample size, especially during the follow-up. However, the percentage of patients lost to follow-up is comparable to previous publications and furthermore there were no differences between those lost and those that completed the follow-up. Further and larger prospective studies to validate the prognostic role of the 895 DSC threshold should be considered. Sec- ondly, the present study cannot establish the direction of the relationships among PA and its predictors. Thirdly, our study population came from a specific geographical area and our results cannot be generalized to countries with different cultural determinants. Despite these limi- tations, our study had many strengths. It is multicentric and has included a wide range of variables as potential PA predictors, reflecting physiological, psychological and QoL aspects in IPF patients. Finally, we explored other predictors of PA variables beyond DSC, such as PA inten- sity and sedentary behaviour. Conclusions In summary, our study identifies muscle strength and psychological factors as novel PA predictors in IPF, being both modifiable factors with interventions. These findings suggest potential aspects that can be targeted to improve PA in IPF patients from the diag- nosis, and support the need for early inclusion in rehabilitation programs, including respiratory and peripheral muscle training. Moreover, psychological assessment should be considered. Finally, it describes change in DSC as a potential progression or mortality predictor in IPF, suggesting that PA monitoring could be a complementary marker of progression to lung function and exercise capacity, which should be con- sidered in clinical practice. Further longitudinal stud- ies are needed to study the predictors of PA changes and in its prognostic role in IPF, beyond traditional prognostic factors. Abbreviations 6MWD: Six‑minute walked distance; 6MWT: Six‑minute walking test; BMI: Body mass index; DLCO: Carbon monoxide diffusing capacity; DSC: Daily step count; FFMI: Fat‑free mass index; FVC: Forced vital capacity; GAP: Gender‑ age‑physiology; HADS: Hospital anxiety and depression scale; HRCT : High resolution computed tomography; ILD: Interstitial lung disease; IPF: Idiopathic pulmonary fibrosis; MEP: Maximum expiratory pressure; METS: Metabolic equivalents; MIP: Maximum inspiratory pressure; mMRC: Modified medical research council; MVPA: Moderate to vigorous physical activity; PA: Physical activity; PAL: Physical activity level; PFTs: Pulmonary function tests; QMVC: Quadriceps maximum voluntary contraction; HRQoL: Health‑related quality of life; SGRQ: Saint George respiratory questionnaire. Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s12890‑ 022‑ 02134‑4. Additional file 1: Table S1. General characteristics of subjects that com‑ pleted and not completed follow‑up. Additional file 2: Table S2. Longitudinal changes in lung function, exer‑ cise capacity, muscle strength, body mass and composition, dyspnoea, quality of life and psychological factors in IPF patients (n=22). Additional file 3: Table S3. General characteristics at baseline of subjects that completed follow‑up by progression‑free survival** at 24 months (n=22). Additional file 4: Table S4. Longitudinal characteristics (changes in parameters) * by progression‑free survival** at 24 months. Acknowledgements Laura Gutiérrez Martín and Concepción Ballano Castro. Respiratory Medicine Department, Hospital del Mar, Barcelona, Spain. Author contributions DB‑B, PhD: Design and methodology, acquisition of funding, visits perfor‑ mance, data collection, data analysis and writing. AR‑P, Physiotherapist: Visits performance, data collection and writing. DCV, PhD: Design and methodol‑ ogy, expertise and feedback. VV‑Z, PhD: Design and methodology, expertise and feedback. GB, MD: Design and methodology, expertise and feedback. FH‑G, PhD: Design and methodology, expertise and feedback. KP, PhD: Design and methodology, expertise and feedback. JML, PhD: Expertise, writing and feedback. RC, PhD: Expertise, writing and feedback. OAC, MD: Expertise, writ‑ ing and feedback; JS, PhD: Design and methodology, expertise and feedback. MM‑M, PhD: Design and methodology, expertise and feedback. XD, Statistic: Data analysis. JG, PhD: Expertise, feedback, acquisition of funding and writ‑ ing. DAR, PhD: Design and methodology, expertise, feedback, acquisition of funding and writing. EB, PhD: Design and methodology, expertise, feedback, acquisition of funding and writing. All authors read and approved the final manuscript. Funding This study was supported by SEPAR 2017 (Fellowship) and Rio Hortega; ISCIII (Project and fellowship). Page 8 of 9Badenes‑Bonet et al. BMC Pulmonary Medicine (2022) 22:340 Availability of data and materials The datasets supporting the conclusions of this article are included within the article (and its additional files). Further enquiries can be directed to the corresponding author. Declarations Ethics approval and consent to participate This study protocol was reviewed and approved by the local ethics committee CEIC‑PSMar (Comité Ético de Investigación Clínica‑ Parc de Salut Mar), Bar‑ celona, Spain with approval number 2017/7241/I, and carried out according to the principles of the Declaration of Helsinki for human investigations. All participants signed the appropriate informed consent prior to their inclusion. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests related to the manuscript. Author details 1 Interstitial Lung Disease Unit, Respiratory Medicine Department, Hospital del Mar, Passeig Marítim 25, 08003 Barcelona, Spain. 2 Department of Medi‑ cine and Life Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain. 3 Centro de Investigación en Red de Enfermedades Respiratorias, (CIBERES), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain. 4 IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. 5 Respiratory Medicine Depart‑ ment, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 6 Respiratory Medicine Department, IDIBELL, Hospital Universitari de Bellvitge, Barcelona, Spain. 7 Respiratory Medicine Department, Hospital Clínic, Barcelona, Spain. 8 Respiratory Medicine Department, Hospital Germans Trias i Pujol, Barcelona, Spain. 9 Scientific, Statistics and Technical Department, Hospital del Mar‑IMIM, Barcelona, Spain. Received: 3 May 2022 Accepted: 22 August 2022 References 1. Raghu G, Remy‑Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, et al. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018;198:e44–68. 2. Molgat‑Seon Y, Schaeffer MR, Ryerson CJ, Guenette JA. Exercise patho‑ physiology in interstitial lung disease. Clin Chest Med. 2019;40:405–20. 3. Nakayama M, Bando M, Araki K, Sekine T, Kurosaki F, Sawata T, et al. Physi‑ cal activity in patients with idiopathic pulmonary fibrosis. Respirology. 2015;20(4):640–6. 4. Wallaert B, Monge E, Le Rouzic O, Wémeau‑Stervinou L, Salleron J, Gros‑ bois JM. Physical activity in daily life of patients with fibrotic idiopathic interstitial pneumonia. Chest. 2013;144(5):1652–8. 5. Bahmer T, Kirsten AM, Waschki B, Rabe KF, Magnussen H, Kirsten D, et al. Clinical Correlates of Reduced Physical Activity in Idiopathic Pulmonary Fibrosis. Respiration. 2016;91(6):497–502. 6. Bahmer T, Kirsten AM, Waschki B, Rabe KF, Magnussen H, Kirsten D, et al. Prognosis and longitudinal changes of physical activity in idiopathic pulmonary fibrosis. BMC Pulm Med. 2017;17(1):104. 7. Prasad JD, Paul E, Holland AE, Glaspole IN, Westall GP. Physical activity decline is disproportionate to decline in pulmonary physiology in IPF. Respirology. 2021;26(12):1152–9. 8. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of echocardiography. Endorsed by the European Association of echocardiography, a registered branch of the European Society of cardiology. J Am Soc Echocardiogr. 2010;23(7):685–713. 9. Sehgal S, Small B, Highland KB. Activity monitors in pulmonary disease. Respir Med. 2019;151:81–95. 10. Waschki B, Kirsten A, Holz O, Müller KC, Meyer T, Watz H, et al. Physical activity is the strongest predictor of all‑cause mortality in patients with COPD: a prospective cohort study. Chest. 2011;140(2):331–42. 11. Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, Franklin BA, et al. Physical activity and public health: updated recommendation for adults from the American college of sports medicine and the American Heart Associa‑ tion. Med Sci Sports Exerc. 2007;39(8):1423–34. 12. Watz H, Waschki B, Meyer T, Magnussen H. Physical activity in patients with COPD. Eur Respir J. 2009;33(2):262–72. 13. Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Useful‑ ness of the medical research council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax. 1999;54(7):581–6. 14. Jones PW, Quirk FH, Baveystock CM. The St George’s respiratory question‑ naire. Respir Med. 1991;85:25–31. 15. Zigmond AS, Snalth RP. The hospital anxiety and depression scale. Acta psychiatr scand. 2014;64(5):361–70. 16. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. Eur Respir J. 2005;26(2):319–38. 17. Macintyre N, Crapo RO, Viegi G, Johnson DC, van der Grinten CPM, Brusasco V, et al. Standardisation of the single‑breath determination of carbon monoxide uptake in the lung. Eur Respir J. 2005;26(4):720–35. 18. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six‑minute walk test. Am J Respir Crit Care Med. 2002;166(1):111–7. 19. Robles PG, Mathur S, Janaudis‑Fereira T, Dolmage TE, Goldstein RS, Brooks D. Measurement of peripheral muscle strength in individuals with chronic obstructive pulmonary disease: A systematic review. J Cardiopulm Reha‑ bil Prev. 2011;31(1):11–24. 20. Gosselink R, Troosters T, Decramer M. Peripheral muscle weakness con‑ tributes to exercise limitation in COPD. Pneumologie. 1996;50(8):551–2. 21. Luna‑Heredia E, Martín‑Peña G, Ruiz‑Galiana J. Handgrip dynamometry in healthy adults. Clin Nutr. 2005;24(2):250–8. 22. Morales P, Sanchis J, Cordero PJ, Díez JL. Maximum static respiratory pres‑ sures in adults. Reference values for a Caucasian Mediterranean popula‑ tion. Arch Bronconeumol. 1997;33(5):213–9. 23. Flaherty KR, Brown KK, Wells AU, Clerisme‑Beaty E, Collard HR, Cottin V, et al. Design of the PF‑ILD trial: A double‑blind, randomised, placebo‑ controlled phase III trial of nintedanib in patients with progressive fibros‑ ing interstitial lung disease. BMJ Open Respir Res. 2017;4(1):1–7. 24. Cottin V, Hirani NA, Hotchkin DL, Nambiar AM, Ogura T, Otaola M, et al. Presentation, diagnosis and clinical course of the spectrum of progres‑ sive‑fibrosing interstitial lung diseases. Eur Respir Rev. 2018;27(150): 180076. 25. Cut‑off finder. https:// molpa thohe idelb erg. shiny apps. io/ Cutoff Find er_ v1/. 26. Nishiyama O, Yamazaki R, Sano H, Iwanaga T, Higashimoto Y, Kume H, et al. Physical activity in daily life in patients with idiopathic pulmonary fibrosis. Respir Investig. 2018;56(1):57–63. 27. Xavier RF, Pereira ACAC, Lopes AC, Cavalheri V, Pinto RMC, Cukier A, et al. Identification of phenotypes in people with COPD: influence of physical activity, sedentary behaviour, body composition and skeletal muscle strength. Lung. 2019;197(1):37–45. 28. Gea J, Agustí A, Roca J. Pathophysiology of muscle dysfunction in COPD. J Appl Physiol. 2013;114(9):1222–34. 29. Nishiyama O, Taniguchi H, Kondoh Y, Kimura T, Ogawa T, Watanabe F, Ari‑ zono S. Quadriceps weakness is related to exercise capacity in idiopathic pulmonary fibrosis. Chest. 2005;127(6):2028–33. 30. Guler SA, Hur SA, Lear SA, Camp PG, Ryerson CJ. Body composition, mus‑ cle function, and physical performance in fibrotic interstitial lung disease: a prospective cohort study. Respir Res. 2019;20(1):56. 31. Panagiotou M, Polychronopoulos V, Strange C. Respiratory and lower limb muscle function in interstitial lung disease. Chron Respir Dis. 2016;13(2):162–72. 32. De Troyer A, Yernault JC. Inspiratory muscle force in normal subjects and patients with interstitial lung disease. Thorax. 1980;35(2):92–100. 33. Laveneziana P. Qualitative aspects of exertional dyspnea in patients with restrictive lung disease. Multidiscip Respir Med. 2010;5(3):211–5. 34. Santana PV, Cardenas LZ, De Albuquerque ALP, De Carvalho CRR, Caruso P. Diaphragmatic ultrasound findings correlate with dyspnea, exercise Page 9 of 9Badenes‑Bonet et al. BMC Pulmonary Medicine (2022) 22:340 • fast, convenient online submission • thorough peer review by experienced researchers in your field • rapid publication on acceptance • support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year • At BMC, research is always in progress. Learn more biomedcentral.com/submissions Ready to submit your research ? Choose BMC and benefit from: tolerance, health‑related quality of life and lung function in patients with fibrotic interstitial lung disease. BMC Pulm Med. 2019;19(1):1–10. 35. Dueñas‑Espín I, Demeyer H, Gimeno‑Santos E, Polkey MI, Hopkin‑ son NS, Rabinovich RA, et al. Depression symptoms reduce physical activity in COPD patients: a prospective multicenter study. Int J COPD. 2016;11(1):1287–95. 36. Hur SA, Guler SA, Khalil N, Camp PG, Guenette JA, Ryerson CJ. Impact of psychological deficits and pain on physical activity of patients with interstitial lung disease. Lung. 2019;197(4):415–25. 37. Shingai K, Matsuda T, Kondoh Y, Kimura T, Kataoka K, Yokoyama T, et al. Cutoff points for step count to predict 1 year all‑cause mor‑ tality in patients with idiopathic pulmonary fibrosis. Respiration. 2021;100(2):1151–7. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in pub‑ lished maps and institutional affiliations.