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. 2024 Nov 21;19(11):e0313209. doi: 10.1371/journal.pone.0313209

Reference values for respiratory muscle strength and maximal voluntary ventilation in the Brazilian adult population: A multicentric study

Palomma Russelly Saldanha Araújo 1,2, Jéssica Danielle Medeiros da Fonseca 1,2, Ana Aline Marcelino 1,2, Marlene Aparecida Moreno 3, Arméle de Fátima Dornelas de Andrade 4, Matias Otto Yañez 5, Rodrigo Torres-Castro 6, Vanessa Regiane Resqueti 1,2, Guilherme Augusto de Freitas Fregonezi 1,2,*
Editor: Ming-Ching Lee7
PMCID: PMC11581219  PMID: 39570848

Abstract

Aim

To determine reference values and propose prediction equations for respiratory muscle strength, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and endurance by means of maximal voluntary ventilation (MVV) in healthy Brazilian adults.

Methods

Anthropometric data, level of physical activity, pulmonary function, and respiratory muscle strength and maximal voluntary ventilation of 243 participants (111 men and 132 women) aged 20 to 80 years were assessed at three cities in the southeast and northeast region of Brazil.

Results

Mean maximal respiratory pressures and MVV were higher in men (MIP = 111.0 ± 28.0; MEP = 149.6 ± 40.3; MVV = 150.6 ± 35.2) than in women (MIP = 87.9 ± 17.6; MEP = 106.7 ± 25.2; MVV = 103.4 ± 23.2; all p < 0.05). Based on regression models, the following prediction equations were proposed for men: MIP = 137–0.57 (age), R2 = 0.13, standard error of estimate (SEE) = 26.11; MEP = 179.9–0.67 x (age), R2 = 0.08, SEE = 38.54; and MVV = 206.3–1.18 x (age), R2 = 0.36, SEE = 28.08. Prediction equations were also proposed for women: MIP = 107.3–0.4 x (age), R2 = 0.16, SEE = 16.10; MEP = 127.4–0.43 x (age), R2 = 0.08, SEE = 24.09; and MVV = 146.3–0.86 x (age), R2 = 0.42, SEE = 17.56.

Conclusion

Reference values for MIP, MEP, and MVV were determined in healthy Brazilian adults. Results from different Brazilian regions provided adequate prediction equations considering an ethnically heterogeneous population.

Introduction

The assessment of pulmonary function, strength and maximal voluntary ventilation of respiratory muscles allows monitoring respiratory diseases, early detection of respiratory muscle weakness and fatigue, and prognostic and predictive information on patient survival [14].

Respiratory muscle strength is commonly assessed using maximal respiratory pressure (MRP) (i.e., maximal inspiratory pressure [MIP] and maximal expiratory pressure [MEP]) [5]. Respiratory muscle endurance is assessed using maximal voluntary ventilation (MVV) [6]. The validity of MVV in assessing respiratory endurance during brief 12 or 15-second test is uncertain [5, 6]. Nevertheless, this maneuver assesses maximum ventilatory capacity, reflecting the functioning of the inspiratory pump and chest wall [7]. It is actually clinically utilized the most to determine ventilatory reserve [8, 9], assess risk of postoperative complications [10] and establish targets for muscle training [11]. These effort-dependent and noninvasive assessments are easy to apply and commonly used to diagnose and monitor patient progression [12, 13].

Reference values allow comparing assessment results and expected values according to specific biological characteristics of a population [14]. Nevertheless, technical, individual, and population differences may lead to variability in reference values and prediction equations [13]. Although previous studies suggested prediction equations for MIP, MEP, and MVV in the Brazilian population [12, 1517], were based on the local population, not multicenter studies. Moreover, there is methodological variability regarding MIP, MEP, and MVV data. Many MIP and MEP studies used less accurate and not recommended mechanical devices, since the nineties, to study respiratory muscle strength [12, 16, 17]. In fact, guidelines recommend the use of a digital manometer with high precision [18]. Regarding MVV, the only study that offers reference values for this variable was conducted at a single center [12]. Therefore, there is a need to update these values.

We aim to establish new reference values for MIP and MEP, as well as MVV, in a diverse sample of healthy Brazilian adults aged 20 to 80 years, residing in three different cities in Brazil. In addition to these primary objectives, our research endeavors to explore potential variations in these respiratory parameters across sex and age groups. By doing so, we aim to not only provide updated and relevant benchmarks for clinical and research purposes but also to propose comprehensive prediction equations specifically tailored to the unique characteristics of the Brazilian population. These new equations will improve our understanding of respiratory health and provide better guidance for diagnostic and treatment approaches. In addition, we will compare the values resulting from our generated equation with those obtained from previously published equations.

Methods

Study type and sample

This multicenter cross-sectional study was conducted between September 01, 2009 and December 25, 2011 at three cities in Brazil: Natal (Rio Grande do Norte), Recife (Pernambuco), and Piracicaba (São Paulo). This study was reported following the “Strengthening the Reporting of Observational Studies in Epidemiology” (STROBE) statement [19].

Participants were recruited by convenience through publicity to university students at each center, as well as via social media and invited to participate according to the following inclusion criteria: self-reported healthy Brazilian individuals; age between 20 and 80 years; body mass index (BMI) between 18.5 and 29.9 kg/m2; non-smoker; non-pregnant; without respiratory, neuromuscular, cerebrovascular, orthopedic, or cardiac diseases; with normal pulmonary function (i.e., forced vital capacity [FVC] > 80% and ratio between forced expiratory volume in the first second [FEV1] and FVC > 0.7 or > 85% of predicted), without any acute respiratory symptoms in the last month [20]. Those who had difficulty performing tests or quit the study were excluded. Participants had no previous contact with respiratory muscle strength assessments.

This study was approved by the research university ethics committee numbers 260/08. All participants were informed about the objectives and methods of the study and signed written the informed consent form. The data from this study is part of an umbrella study, a portion of which was previously published [21].

Study design

Participants were divided into six age groups (20 to 29, 30 to 39, 40 to 49, 50 to 59, 60 to 69, and 70 to 80 years), each group was divided according to sex (men and women), totaling 12 groups. Assessments were conducted in two stages. The first stages included a structured interview (sociodemographic data and previous diseases), anthropometry data (weight, height, and Body Mass Index–BMI), and spirometry. The second stage took place following a 30-minute rest period, during which participants underwent MRP and MVV assessments and completed a questionnaire on habitual physical activity (HPA). The order of respiratory assessments was randomized, respecting the 20-minute interval between them. The same previously trained evaluator at each research center conducted both stages on the same day. Fig 1 illustrates the study flowchart.

Fig 1. Study flowchart.

Fig 1

Anthropometric variables

Weight was measured using an anthropometric scale (model 31, Filizola®, São Paulo, Brazil), whereas height was assessed during maximum inspiration using a stadiometer integrated into the scale (1 mm precision Participants were measured wearing light clothing and were barefoot. BMI was calculated considering the ratio between weight and height squared (kg/m2) and classified according to the World Health Organization (WHO) [22].

Spirometry

Pulmonary function and endurance were assessed through FVC and MVV, respectively, using a DATOSPIR-120C® spirometer (Sibelmed®, Barcelona, Spain), according to the American Thoracic Society / European Respiratory Society (ATS/ERS) [23]. FVC, FEV1, and FEV1/FVC ratio were analyzed as absolute and reference values for the Brazilian population [20]. Participants performed assessments seated on a chair with backrest and feet supported on the floor.

During FVC, participants performed a maximal inspiration until total lung capacity, followed by a complete, fast, and vigorous expiration until residual volume. The assessment was repeated three to five times after one-minute intervals and considered acceptable when the difference between the two largest FVC and FEV1 values varied less than ≤0.150 L [23]. For MVV assessment, participants were asked to breathe as fast and deep as possible above the tidal volume and below the vital capacity for 15 seconds. At least two acceptable measurements were obtained (< 10% of variation), and the highest value was recorded, extrapolating the accumulated volume from 15 seconds to 1 minute [24].

Respiratory muscle strength

Respiratory muscle strength was measured using a digital manometer (MicroRPM, CareFusion, UK), following the European Respiratory Society guidelines [5]. The PUMA PC software (Micro Medical, Rochester Kent, UK) operationalized the MIP and MEP (equivalent to MEP) variables using the aforementioned maximum mean pressures. Participants performed a maximum inspiration from residual volume for MIP and a maximum expiration from total lung capacity for MEP, performing 3–5 maneuvers, with a 1 minute break between them. Both were assessed with participants using a disposable flanged mouthpiece and a nose clip. A minimum of three reproducible and acceptable measurements were performed; if the last maneuver was the highest, a new maneuver should be performed, and variability should not exceed 10%. The highest value of maximum pressure sustained was selected.

Level of physical activity

The level of physical activity was assessed using the Brazilian version of the Baecke Habitual Physical Activity–HPA questionnaire [25]. This version has eight questions and covers two physical activity components performed in the last 12 months: 1) physical exercises in leisure (PEL, with four questions) and 2) leisure and locomotion activities excluding physical exercises (LLA, with four questions). Answers were scored using a Likert scale (0 to 5), and PEL and LLA scores average (Q1 + Q2 + Q3 + Q4 / 4) correspond to the respective scores. The average of scores (PEL + LLA/2) represented the HPA index [25]. For analysis we select the average of values of the HPA index.

Statistical analysis and sample size calculation

A pilot study with 29 women and 32 men was used to calculated the sample size based on the effect size (R2) of regression analysis for MIP, MEP, and MVV variables found by Neder et al. [12] and considering a power of 99% and alpha error of 0.05. These values were determined for each center (i.e., 183 participants; 87 women and 96 men) and doubled to minimize exclusions due to data acquisition errors or dropouts. The total sample size was estimated as 366 participants to be distributes across for all centers.

Data were expressed as mean ± standard deviation. The Kolmogorov-Smirnov test verified data normality. Unpaired t-test and ordinary one-way ANOVA compared MIP, MEP, and MVV between sex and age groups, respectively; the Newman-Keuls post-hoc test was used in case of statistical significance between age groups. Linear Pearson’s correlation coefficient (r) assessed relationships between dependent (MIP, MEP, and MVV) and independent variables (age, weight, height, BMI, and HPA). Independent variables with statistical significance were included in the linear regressions for MIP, MEP, and MVV. Lower limits were calculated from the fifth percentile of residuals using a normal distribution according to the following equation: lower limit = predicted value– 1.645 x standard error of estimate (SEE) [18]. The SPSS software (IBM Corp., version 15.0, NY, USA) analyzed data considering p < 0.05 and 95% confidence intervals.

Results

A total of 324 participants were recruited, and 244 were included in the study (Fig 1). One participant dropped out of the study; thus, 243 participants (111 men and 132 women) performed the MRP. Of these, 32 could not perform MVV (i.e non-reproducible tests, characterized by >10% variation and/or inability to perform the test in less than 12 seconds), totaling 211 participants (110 men and 111 women) for this measurement.

Characterization of sample

Table 1 shown the mean age, anthropometric data, and HPA. Table 2 presents pulmonary function divided by sex. MIP, MEP, and MVV separated by sex and age are described in Table 3.

Table 1. Characterization of individuals who performed MRP and MVV assessments.

Age groups (years) Anthropometric data
Age (years) Weight (Kg) Height (m) BMI (Kg/m2) HPA
MRP
Men (n = 111)
20 to 29 (n = 27) 22.1 ± 2.2 73.9 ± 10.6 1.75 ± 0.09 24.1 ± 2.4 5.2 ± 1.3
30 to 39 (n = 19) 34.4 ± 3.4 76.3 ± 8.5 1.75 ± 0.04 25.0 ± 2.6 4.8 ± 1.3
40 to 49 (n = 19) 44.2 ± 2.6 75.6 ± 9 1.70 ± 0.06 26.0 ± 2.6 5.0 ± 1.7
50 to 59 (n = 16) 53.4 ± 2.8 77.1 ± 10.8 1.72 ± 0.06 26.0 ± 2.9 5.2 ± 1.2
60 to 69 (n = 16) 63.9 ± 2.6 74.6 ± 9 1.65 ± 0.09 27.4 ± 1.7 5.1 ± 1.6
70 to 80 (n = 14) 74.6 ± 4.0 71.4 ± 7.2 1.66 ± 0.08 26.0 ± 2.1 4.7 ± 1.0
Women (n = 132)
20 to 29 (n = 25) 23.2 ± 3.3 61.9 ± 10.8 1.65 ± 0.06 22.8 ± 3.3 4.7 ± 0.1
30 to 39 (n = 20) 33.5 ± 3.2 62.6 ± 7.4 1.63 ± 0.05 23.6 ± 2.2 4.4 ± 1.2
40 to 49 (n = 24) 45.1 ± 3.4 63.6 ± 9.7 1.60 ± 0.07 24.9 ± 3.5 4.5 ± 1.5
50 to 59 (n = 24) 54.5 ± 3.5 63.3 ± 7.3 1.58 ± 0.06 25.5 ± 2.9 4.5 ± 1.3
60 to 69 (n = 19) 64.3 ± 3.1 65.2 ± 8.1 1.57 ± 0.07 26.5 ± 2.8 4.6 ± 1.2
70 to 80 (n = 20) 74.8 ± 3.2 65.2 ± 9.3 1.58 ± 0.07 25.9 ± 2.7 4.6 ± 0.8
MVV
Men (n = 100)
20 to 29 (n = 20) 21.8 ± 2.3 74.5 ± 9.7 1.77 ± 0.08 23.8 ± 2.4 5.0 ± 1.3
30 to 39 (n = 18) 34.6 ± 3.4 76.5 ± 8.7 1.75 ± 0.04 25.1 ± 2.6 4.8 ± 1.3
40 to 49 (n = 17) 44.5 ± 2.6 76.1 ± 9 1.71 ± 0.07 26.1 ± 2.6 5.1 ± 1.8
50 to 59 (n = 15) 53.6 ± 2.8 77.6 ± 11.0 1.72 ± 0.06 26.1 ± 3.0 5.1 ± 1.2
60 to 69 (n = 16) 63.9 ± 2.6 74.6 ± 9.0 1.65 ± 0.09 27.4 ± 1.7 5.1 ± 1.6
70 to 80 (n = 14) 74.6 ± 4.0 71.4 ± 7.2 1.66 ± 0.08 26.0 ± 2.1 4.7 ± 1.0
Women (n = 111)
20 to 29 (n = 18) 23.9 ± 3.6 59.5 ± 9.6 1.65 ± 0.05 22.0 ± 2.8 4.5 ± 1.0
30 to 39 (n = 18) 33.8 ± 3.1 62.2 ± 7.3 1.63 ± 0.06 23.4 ± 2.1 4.4 ± 1.2
40 to 49 (n = 19) 45.6 ± 3.2 65.0 ± 9.8 1.61 ± 0.07 25.0 ± 3.6 4.5 ± 1.4
50 to 59 (n = 19) 53.9 ± 3.5 63.1 ± 7.0 1.59 ± 0.07 25.2 ± 2.9 4.5 ± 1.3
60 to 69 (n = 17) 64.1 ± 3.1 64.8 ± 8.5 1.57 ± 0.07 26.2 ± 2.8 4.6 ± 1.2
70 to 80 (n = 20) 74.8 ± 3.2 65.1 ± 9.3 1.58 ± 0.07 25.9 ± 2.7 4.6 ± 0.8

Data presented as mean ± standard deviation. BMI: body mass index. MVV: maximal voluntary ventilation. MRP: maximal respiratory pressure. HPA: Habitual Physical Activity.

Table 2. Pulmonary function of participants who performed MRP and MVV assessments.

Variables MRP MVV
Men Women Men Women
FVC (L) 4.4 ± 0.8 3.1 ± 0.6 4.4 ± 0.9 3.1 ± 0.6
FVC (% predicted) 92.1 ± 10 95.2 ± 13.6 93.1 ± 9.7 95.3 ± 11.7
FEV1 (L) 3.7 ± 0.7 2.7 ± 0.6 3.7 ± 0.7 2.7 ± 0.6
FEV1 (% predicted) 95.5 ± 11.3 99.1 ± 14.3 97.3 ± 10.1 100.8 ± 13.4
FEV1/FVC ratio 0.84 ± 0.1 0.85 ± 0.1 0.84 ± 0.1 0.85 ± 0.1
FEV1/FVC ratio (% predicted) 104 ± 8.3 101 ± 12.9 104.9 ± 7.7 105 ± 8.5

Data presented as mean ± standard deviation. FVC: forced vital capacity. FEV1: forced expiratory volume in the first second. MVV: maximal voluntary ventilation. MRP: maximal respiratory pressure. L: liters.

Table 3. MRP and MVV by age and sex.

Age (years) Men Women
MIP MEP MVV MIP MEP MVV
(cmH2O) (cmH2O) (L) (cmH2O) (cmH2O) (L)
n = 111 n = 111 n = 100 n = 132 n = 132 n = 111
20 to 29 119.2 ± 33.7 152.6 ± 47.8 168.2 ± 36.0 96.9 ± 14 117 ± 27.7 123.9 ± 14.0
30 to 39 126.8 ± 23.5 169.1 ± 38 173.3 ± 26.3 94.5 ± 18.3 112 ± 19.8 118.5 ± 25.3
40to 49 115.6 ± 26.3 164.1 ± 42.8 157.7 ± 25.2 90.2 ± 16.7 115.1 ± 26.1 112.5 ± 16.2
50 to 59 107.6 ± 16.2 150.2 ± 26.4 158.4 ± 22.0 82.7 ± 17 95.4 ± 23.7 96.6 ± 17.0
60 to 69 91.7 ± 17.7 131.8 ± 30.2 124.7 ± 23.6 83.2 ± 19.7 103.3 ± 26.5 84.9 ± 15.5
70 to 80 93.9 ± 25.6 117.1 ± 18.6 109.0 ± 26.3 78.1 ± 13.4 95.8 ± 17.1 85.1 ± 14.7
20 to 80 111.0 ± 28.0 149.6 ± 40.3 150.6 ± 35.2 87.9 ± 17.6 106.7 ± 25.2 103.4 ± 23.2

Data presented as mean ± standard deviation. MIP: maximal inspiratory pressure. MEP: maximal expiratory pressure. MVV: maximal voluntary ventilation. L: liters. cmH2O: centimeters of water.

Prediction equations

Age was negatively correlated with MRP and MVV in men (MIP: r = − 0.37; MEP: r = − 0.30; MVV: r = − 0.60; p < 0.001) and women (MIP: r = − 0.40; MEP: r = − 0.30; MVV: r = − 0.65; p < 0.001) (Table 4). However, the MRP of both sexes was not correlated with weight, height, BMI, and HPA. On the other hand, MVV was positively correlated with height in women (r = 0.44; p = 0.02).

Table 4. Prediction equations for MRP and MVV in Brazilian adults.

Prediction equations R2 SEE LLN
MIP (cmH2O) Men 137–0.57 x (age) 0.13 26.11 MIPpredicted–42.95
Women 107.3–0.4 x (age) 0.16 16.10 MIPpredicted–26.48
MEP (cmH2O) Men 179.9–0.67 x (age) 0.08 38.54 MEPpredicted–63.4
Women 127.4–0.43 0.08 24.09 MEPpredicted–39.63
MVV (L) Men 206.3–1.18 x (age) 0.36 28.08 MVVpredicted–46.19
Women 146.3–0.86 x (age) 0.42 17.56 MVVpredicted–28.89

MIP: maximal inspiratory pressure. MEP: maximal expiratory pressure. MVV: maximal voluntary ventilation. L: liters. cmH2O: centimeters of water. R2: coefficients of determination adjusted. SEE: standard error of estimate. LLN: lower limit of normal.

Age was included in linear regressions for MIP, MEP, and MVV for men and women. The prediction equations for MRP and MVV in Brazilian adults aged between 20 and 80 years were established. The prediction equations for MRP and MVV in Brazilian adults aged between 20 and 80 years were established, and the coefficients of determination adjusted (R2), standard error of estimate (SEE), and lower limit of normal (LLN) for sex are shown in Table 4.

Comparation with previously published equations

The S1 Table describes previous studies that established prediction equations for MRP [12, 1517] and MVV [12] in the Brazilian adult population. Also, Fig 2 shows MIP, MEP, and MVV values divided by sex and compared with reference values from previous studies.

Fig 2. Line of best fit for values observed in the study and predicted values of maximal respiratory pressure and maximal voluntary ventilation from previous studies.

Fig 2

Discussion

The main findings of this multicentric study was to establish reference values for MIP, MEP, and MVV and propose prediction equations for the healthy Brazilian population aged between 20 and 80 years. The following results were observed: 1) prediction equations were established for MIP, MEP, and MVV in the Brazilian population; 2) age was negatively correlated with MRP and MVV; and 3) men had higher MRP and MVV values than women.

This was the first Brazilian study establishing prediction equations for MRP and MVV based on a multicentric sample, allowing the representation of an ethnically heterogeneous population. Previous studies were conducted in a single Brazilian region [12, 1517] and may not represent the ethnographic variability from different Brazilian regions.

Brazil is a mixed country, being considered one of the most heterogeneous populations in the world [26]. Being the result of colonization and consequent interethnic crossing between Europeans, represented mainly by the Portuguese, African slaves and native Amerindians [26], in addition to the native population, the indigenous people. This results in variations in skin pigmentation [27]. According to the Brazilian Institute of Geography and Statistics–IBGE [28], in its last census publication, in 2020, Brazil presents a varied racial distribution with 45.35% of Brazilians self-declaring brown, followed by 43.36% white, 10.17%, black, 0.60% indigenous and 0.42% yellow, with the first three classifications covering 99% of the general population. When analyzing the regions of Brazil, the South has the highest number of self-declared white people with 72.58%, followed by 21.71% mixed race, 5.03% black, 0.40% yellow and 0.24% indigenous; The Southeast is 49.88% white, 38.70% mixed race, 10.61% black, 0.67% yellow and 0.13% indigenous; The Northeast has 59.57% mixed race, 26.66% white, 13.04% black, 0.13% yellow and 0.60% indigenous; The North is 20.74% white, 67.16% brown, 8.82% black, 0.17% yellow and 3.11% indigenous; The Midwest has 37.04% white, 52.40% mixed race, 9.15% black, 0.37% yellow and 1.04% indigenous. Our study evaluated three centers, distributed in 2 regions, Northeast and Southeast, with both having a larger population self-declared as white and mixed race.

The significance of tailoring reference values adapting to the local population cannot be underestimated [29]. When evaluating endurance or strength of respiratory muscles, using standardized values based on data not updated, measured with not recommended devices or from other populations may not accurately reflect the unique characteristics and diversities of the Brazilian population. Elements such as genetics, lifestyle, culture, and environmental influences can exert a substantial effect on the health and performance of individuals [30, 31]. Therefore, it is imperative to establish specific reference values that are tailored to the demographics of a particular region or population [30].

We followed international [5] and national [32] guidelines, which recommend equipment high precision for obtaining MIP, MEP, and MVV measures [18]. Neder et al. [12], Simões et al. [16], and Costa et al. [17] used an aneroid manometer, which has low precision and high variability, different from dedicated software and computers connected to devices based on pressure transducers [5]. Also, Pessoa et al. [15] used a similar methodology to calculate reference values for MIP and MEP in individuals from Minas Gerais state; however, they used waist circumference for prediction equations, hampering their applicability.

Age was negatively correlated with MRP, corroborating other studies [12, 1517]. MVV was also negatively correlated with age, corroborating studies from Neder et al. [12] and McClaran et al. [33], who observed a 12% reduction of MVV in healthy and active older adults over six years [33]. Aging causes musculoskeletal changes, such as shifts from type II to type I muscle fibers and reduced muscle mass (i.e., sarcopenia) [34], fiber size, strength, and power [35]. In this sense, age can also influence respiratory muscles by reducing diaphragmatic strength due to muscle atrophy and decreased number of type II muscle fibers; therefore, predisposing individuals to diaphragmatic weakness and reduced respiratory muscle strength [36].

Men had higher MRP values than women, corroborating previous studies [12, 1517]. This result may occur since men have greater muscle mass, number of muscle fibers, and proportion of type II fibers than women; type II fibers have more potential to produce strength and power than type I fibers [35]. Moreover, the zone of apposition is lower, and the diaphragm length is approximately 9% shorter in women than in men. As a result, the diaphragm of women generates low esophageal and gastric pressures during breathing (i.e., low diaphragmatic action) [37]. This may be a complementary mechanism for increased respiratory strength and volume in men.

Most previously published reference values for MRP [12, 1517] represented the local sample. In this study, both sexes presented higher MIP values than the reference values proposed by Simões et al. [16] and Pessoa et al. [15], (all p < 0.01). However, MIP was similar to reference values for women (p = 0.54) and lower than values for men (p = 0.01) from the study by Neder et al. [12] and higher than the values for men and lower than the values for women in values from Pessoa et al. [15] (p < 0.01). MEP in both sexes was higher than the reference values proposed by Costa et al. [17], Simões et al., [16] and Neder et al. [12], (all p < 0.01). We could not compare MEP with reference values from Pessoa et al. [15] since they used waist circumference in the prediction equation. MVV was similar to reference values for men (p = 0.32) and lower than values for women (p = 0.02) from the study by Neder et al. [12].

When comparing the values obtained in our sample to those in other studies [12, 1517], we found that only the reference values for MIP in women and MVV in men from the study by Neder et al. [12] were consistent with our results. Factors such as measurement methods, different instruments, and individual biological and population characteristics may have influenced the assessment of pulmonary function [18]. For instance, the study by Neder et al. [12] was conducted in 1999, and subsequent studies have not updated prediction equations. The discrepancies between our study’s findings and others are primarily attributed to biosocial, sociodemographic, and physical changes (e.g., eating habits, urbanization, and sedentary lifestyles) observed in the Brazilian population. Therefore, it is crucial to update these measurements periodically.

Only Neder et al. [12] developed prediction equations for MVV in the Brazilian adult population; therefore, our comparisons were limited to this study since reference values represent a specific ethnic population. Recently, predictive values for MVV were developed by Silva et al. [38]; however, the authors studied Brazilian individuals aged 6 to 17 years. Prediction equations developed in the present study may represent the Brazilian adult population since they were performed in different locations across the country, reflecting ethnic diversity.

Studies proposing prediction values for pulmonary function must not include individuals with restrictive and obstructive disorders. Among previous studies regarding prediction equations for MRP and MVV in the Brazilian population, only Pessoa et al. [15] adopted pulmonary function values as inclusion criteria. Thus, according to respiratory variables, other studies that suggested reference values may not have included a healthy population, leading to selection bias.

Possessing reference values for MVV that apply to clinical practice is essential. The evaluation of MVV offers supplementary insights and holds clinical relevance for healthy individuals and people with diseases [39]. Furthermore, MVV is employed in several assessments, notably in cardiopulmonary exercise testing, a standard procedure for evaluating exercise capacity. This parameter proves invaluable for quantifying ventilatory reserve in patients dealing with respiratory and cardiovascular conditions [40]. By considering this aspect, healthcare professionals can differentiate between cardiovascular and respiratory profiles in exercise intolerance. However, it is imperative to possess reference values for the ventilatory reserve to enhance the comprehension of the exercise response.

The level of physical activity may have also influenced the results. Only Costa et al. [17] assessed the level of physical activity of the sample for calculating prediction equations. Although this variable was not significantly correlated in the present study, the sample was considered homogeneous since we did not include participants with high physical activity levels. Also, BMI within the normal range was considered an inclusion criterion, whereas Neder et al. [12] included obese participants (i.e., BMI > 29.9 kg/m2). Arenaa and Cahalinb [41] assessed cardiorespiratory fitness and respiratory muscle function in obese subjects (BMI ≥30 kg/m2), linking obesity to respiratory muscle dysfunctions that impact vital capacity. These dysfunctions lead to symptoms of exertion and limitations in functional residual capacity. Other studies have also linked increased weight to a reduction in respiratory muscle strength [4244], as well as to a decrease in MVV [43]. Our study was designed to establish prediction equations for MRP and MVV, update pre-established values, and correct methodological errors from previous studies.

While our study adhered to a rigorous methodology, it is important to acknowledge several limitations that warrant consideration. Firstly, due to the multicenter nature of the study, evaluators varied among centers, introducing some degree of inter-observer variability. Additionally, the non-random sampling method employed in this research may limit the generalizability of our findings. Furthermore, it is imperative to highlight the previous period during which data collection occurred, as there was a delay in analyzing the results, which could potentially affect the relevance of the proposed equations. Additionally, it is imperative to highlight the need for additional validation studies encompassing populations from diverse Brazilian regions. Although our study is multicenter in nature, we did not include ethnic variations in our analysis, perhaps limiting the applicability of our prediction equations. Lastly, it is worth noting that our study did not encompass participants aged over 80 years, thereby excluding this segment of the population from our findings. Consequently, the proposed equations may not accurately represent this older demographic. Future research endeavors should strive to bridge this gap by considering the respiratory health of individuals above the age of 80 to provide a more comprehensive insight into this segment of the population.

Conclusions

In conclusion, the reference values for MIP, MEP, MVV established in this study serve as valuable benchmarks for Brazil’s ethnically diverse population. These findings adhere to the guidelines set forth by the European Respiratory Society [5] and the American Thoracic Society / European Respiratory Society (ATS/ERS) [23]. They are not only pertinent in clinical contexts but also serve as essential references for research endeavors involving individuals aged between 20 and 80 years. These standardized values provide a robust foundation for assessing respiratory health and function in a broad cross-section of the Brazilian population, ultimately contributing to more accurate diagnoses and effective treatment strategies.

Supporting information

S1 Table. Description of prediction equations for MRP and MVV from previous studies.

(DOCX)

pone.0313209.s001.docx (29.4KB, docx)
S1 Data

(XLSX)

pone.0313209.s002.xlsx (27.6KB, xlsx)

Data Availability

All relevant data are within the paper and its Supporting information.

Funding Statement

The author(s) received specific funding for this work: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Finance Code 001 - Ms. Ana Aline Marcelino Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), 316937/2021-5 - Mr. Guilherme A. F. Fregonezi Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), 305960/2021-0 - Ms. Vanessa Regiane Resqueti Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), 88887.692599/2022-00 - Ms. Jéssica Danielle Medeiros da Fonseca.

References

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Decision Letter 0

Yongzhong Guo

6 Jun 2024

PONE-D-24-16298

Reference values for maximal respiratory pressure and maximal voluntary ventilation in the brazilian adult population: a multicentric study

PLOS ONE

Dear Dr.  Fregonezi,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we have decided that your manuscript does not meet our criteria for publication and must therefore be rejected.

The main reasons for rejection are as follows: 1.consistency with the reviewer's comments, there are lots important methodological limitations in submission; 2. many similar studies have been reported.

I am sorry that we cannot be more positive on this occasion, but hope that you appreciate the reasons for this decision.

Kind regards,

Yongzhong Guo, Ph.D

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Dear authors,

Thank you very much for your effort and contribution to area. I have some minor suggestions.

1. On page 3 line 71, you should add methods or devices after recommended.

2. On page 4 line 74 you should add the reference of single center.

3. On page 5 line 116, you should write full name of BMI before abbreviation.

4. On page 7 line 162, you should write full name of HPAI before abbreviation.

5. On page 11 line 222 you should add years after 20-80.

6. I think on page 12 line 231-245, on page 13 line 249-254, should be removed and embedded into discussion.

7. In the discussion on two side, woman should be changed into women. on page 12-13

8. You should say 'the main findings of the our study' rather than the following results in the first paragraph of discussion.

9. I think on page 17 line 361-263 should be removed from limitations. You assessed people from three regions it is not limitation.

10. On page 18 line 378 you should add years after 20-80.

All the best wishes.

Reviewer #2: Thank you very much for inviting me to review this original investigation about new reference equations for maximal respiratory pressures (MRP) and maximal voluntary ventilation (MVV) in Brazilian population. Even when several reference equations for MRP exist worldly and specifically in Brazilian adult population, I do believe this paper add value to the existing literature. Congratulation to the research team for the titanic effort done.

However, some minor and also some major concerns should be answered by the authors.

Introduction

First paragraph (lines 51-54): I think references can be reduced in this paragraph.

Lines 59-60: “While the validity of MVV during a 12 or 15-second test of such brief duration is uncertain in reflecting respiratory endurance”. I think the reference 6 (Laveneziana et al., 2019) should be included here. Indeed, the MVV is not recommended anymore by the ERS as an endurance test. That is why I think authors needs to reinforce the potential value of this new reference equations for MVV, both in the introduction and the discussion.

Lines 66-68: “Although previous studies suggested prediction equations for MIP, MEP, and MVV in the Brazilian population, [6, 9, 12-14]” I think reference number 6 is not adequate here. On the other hand, there are more reference equations for MIP and MEP in Brazilian population (i.e.: Sgariboldi et al. (2015) and Sánchez et al., (2018)). I suggest to include them in the introduction and use then after in the discussion to enrich the discussion. I miss reference equations for MVV in Brazilian population in this paragraph.

Lines 76-78: MIP, MEP and MVV were already expanded above, you don´t need to expand the abbreviations again here.

There is an error concept along the manuscript between “gender” and “sex”. Authors mean sex (as a biological variable) and not gender (which is a social identification). Please, correct this error along the manuscript. According to the lasted statement from ERS for pulmonary function sex and gender should not be confounded in reference equations. https://doi.org/10.1183/13993003.01499-2021

Methods

Firstly, is surprising that data were collected between 2009-11 and not published yet. How authors can explain this fact? If we take into account what ERS says about the obsolescence of reference equations (10 years- Eur Respir J. 2005;26(5):948-68) these data are already obsoleted. How authors can defend these values as representative of the actual population?

Some important details are missing in the methods section: 1) Which was the strategy used for recruitment; where they obtain the sample; the strategy was the same in each research center? 2) Which strategies were used to ensure the consistence of the measurements (did evaluators have some training, some quality control was performed, etc.)?

Line 143: “acceptable when measurements varied less than 5% or were equivalent to 200 mL” [19]. In reference 19 (Graham et al 2019) authors state: “FVC repeatability is achieved when the

difference between the largest and the next largest FVC is <0.150 L for patients older than 6 years of age (86) and <0.100 L or 10% of largest FVC, whichever is greater, for those aged 6 years or younger (8, 87). For FEV1 repeatability, the difference between the largest and the next largest FEV1 is <0.150 L for those older than 6 years of age and <0.100 L or 10% of the largest FEV1, whichever is greater, for those aged 6 years or younger” Please, change the reference or change the numbers.

Line 143-147: how many breaths per minute were aimed for the MVV? In reference number 20 (Miller et al., 2005) 90-110 bpm are remarked as ideal.

Lines 149-158: more technical details are needed. For example: which kind of mouthpiece were used; which pressure was used (peak pressure or plateau pressure- I know that MicroRPM measures the plateau but it should be clarified in the paper); was PUMA software used to see the graphs during the measurements; which quality criteria was used regarding the graph shapes; how much each maneuver lasted?; did the participants rest between maneuvers, and between MIP and MEP?; in which order subjects performed the tests (MIP, MEP and MVV), was always the same?

Lines 160-169: Baecke HPA questionnaire was created for adults over 60 years old, but here it was applied for subjects from 20 years old. Did the authors verify the psychometric proprieties of this questionnaire in the youngest? Could you add some reference?

Line 168 (about algorithm for interpretation) needs a reference.

Results

Line 194: the sample size calculation was 366 subjects but the final sample is composed by 243 for MRP and 211 for MVV. How authors explain so the power calculation of this reference equations if they not achieve the sample size?

Please review table 1: the HPA is under the anthropometric data and this is not correct. Moreover, it is highly important to add the number of subjects (n) achieved in each age group (add this information in the table); only them we can have an idea of the representation in each decade.

I would suggest to merge the pulmonary function data with table 1, after all, these data were collected for characterized the sample, right?

Lines 231-245: authors give p value of their new reference values compared with other reference values published in Brazilian population, but I don’t see this nor as an objective of the study or in the data analysis. Please, add this first as a secondary aim and in the data analysis.

Discussion

I would suggest to enrich the discussion with other Brazilian equations (please see comments in introduction section) and also with the comparation of the most recent MRP equations published. Also, I think it is important to discuss about why only age was included in the equations compared with others that include anthropometric data, as for example the BMI.

Line 345-353: why people with high level of physical activity was not included in the study? I did not see this as a selection criterion. So, is this population really a good representation of Brazilian people? Which are the levels of physical activity in healthy Brazilian population nowadays? Please, justify this.

The LLN was not discussed at all.

The value of reference equations for MVV needs to be reinforce taking into account that this test is not longer recommended in the last statement of ERS (Laveneziana et al., 2019).

Conclusions

Lines 372-372: MIP, MEP and MVV were already expanded above, you don´t need to expand the abbreviation again here.

Reviewer #3: The main aim of this research article is clear. The aim is to obtain reference values for MIP, MEP and MVV in healthy Brazilian subjects. The title should have respiratory muscle strength in place of maximal respiratory pressure.

Although the aim is novel, the study itself is not, as this data has been previously collected in Brazil, but not in multiple sites. The Introduction and Methods section have appropriate detail. It would be good to get a better idea of the ethnicity of the cities and participants, and also previous studies. Results are clear and the data is reasonably well presented with tables and graphs.

The Discussion has a satisfactory level of critical analysis, although more can be added. The significance of the study was given and comparisons made with previous studies, and an emphasis the applied nature of this research.

They are no major issues with the methodology or data analysis. This manuscript is well presented. The language and grammar is acceptable, some improvements in grammar could be made. References are correct and relevant.

Corrections/suggestions for the authors are mentioned below:

Abstract – no changes

Intro

1. Line 55 strength (singular not plural).

2. Line 60. Alter: ‘it is actually the most clinically utilized’ to ‘it is actually clinically utilized the most’.

3. Line 68 – reference 6 is an ERS statement, so how is this a previous study giving Brazilian prediction equations?

4. Line 72-73, can you show where in the ERS statement it mentions a digital manometer is recommended?

Methods

1. Line 95. Give more details on how participants were recruited.

2. Line 96, Brazil has varied ethnicities, so how was this measured and taken into account with the data analysis and regression equations?

3. Line 125 was weight and height taken with or without shoes or coats/jackets?

4. Line 135: …(ATS/ERS) recommendations.

5. Line 143 for MVV assessment, was respiratory rate (RR) measured, as this can affect MVV and were subjects guided to a fixed RR or free breathing RR? See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968560/

6. Line 154. Is not a flanged mouthpiece the standard? Could a cylindrical one cause greater leakage?

7. Line 177. so n=366 was the number in total or for each centre?

8. Line 183. Was correlation a linear, logistic or multiple regression?

Results

1. Line 194. 324 were recruited, 244 were included. What happened to the 80 subjects whose data was not collected? Clear from Figure 1, but could say that 80 did not met inclusion criteria.

2. Line 196. Give the reason(s) why 32 could not perform the MVV?

3. Line 199, use term separated and not divided.

4. Line 207/Table 2. Give FVC/FEV1 ratio data to 2 decimal places.

5. Add sub-headings to Results section.

6. Figure 2 – seems images have poor resolution.

7. Did you analyse the differences between the three cities – was there a difference, which might explain the variation in the previous results?

Discussion

1. Line 265 – mention is made of an ethnically heterogenous population, but no evidence in the Methods is given. If this is the case, give an idea of the ethnic background of Brazil and the percentage of your subjects accordingly. Also give the ethnic background of the three different cities.

2. Give more critical analysis on the previous studies – did they report ethnic differences, and what geographical areas did they study, which could have been influenced by ethnicity.

3. Line 279 , where do these recommendations state this.

4. Line 305 – sentence can be written in more clear language.

5. Line 324 – discussion on equipment was given before, so don’t repeat it.

6. Line 351. Does a BMI >25 but <29.9 significantly affect MRP and MVV?

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Reviewer #1: Yes: Ebru CALIK KUTUKCU

Reviewer #2: No

Reviewer #3: Yes: Mirza M F Subhan

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For journal use only: PONEDEC3

PLoS One. 2024 Nov 21;19(11):e0313209. doi: 10.1371/journal.pone.0313209.r003

Author response to Decision Letter 0


21 Aug 2024

Yongzhong Guo, Ph.D Academic Editor

Plos One Natal June 25

Subject: Revision and resubmission of Manuscript PONE-D-24-16298

Dear Editor

Thank you for revising our manuscript. We appreciate the reviewers for their complimentary comments and suggestions. We have revised the manuscript in accordance to the recommendations.

Please find attached a point-by-point response to the reviewer’s comments. We hope that you find our answers satisfactory, and that the manuscript is now acceptable for publication.

Sincerely,

Prof. Dr. Guilherme Augusto de Freitas Fregonezi

RESPONSE TO REVIEWERS

Journal Requirements:

REVIEWER 1

Comments to the Author Dear authors,

Thank you very much for your effort and contribution to area. I have some minor suggestions.

1. On page 3 line 71, you should add methods or devices after recommended.

Author’s: Thank you for your note. We've supplemented the information in the introduction section with the following sentence: “Many MIP and MEP studies used less accurate and not recommended mechanical devices, since the nineties, to study respiratory muscle strength” (page 3, line 73 and 74).

2. On page 4 line 74 you should add the reference of single center.

Author’s: We've supplemented the information in the introduction section by adding the following reference: [12] Neder, J.A., et al., Reference values for lung function tests. II. Maximal respiratory pressures and voluntary ventilation. Braz J Med Biol Res, 1999. 32(6):

p. 719-27. (page 4, line 77).

3. On page 5 line 116, you should write full name of BMI before abbreviation.

Author’s: We've supplemented the information in the methods section with the following sentence: “anthropometry data (weight, height, and Body Mass Index – BMI)” (page 5, line 120 and 121).

4. On page 7 line 162, you should write full name of HPAI before abbreviation.

Author’s: We've add the information in the methods section with the following sentence: “The level of physical activity was assessed using the Brazilian version of the Baecke Habitual Physical Activity – HPA questionnaire” (page 8, line 172).

5. On page 11 line 222 you should add years after 20-80.

Author’s: We've supplemented the information in the results section.

6. I think on page 12 line 231-245, on page 13 line 249-254, should be removed and embedded into discussion.

Author’s: Thank you for your note. The supplementary material presented in the results section was added in the discussion section (page 16 and 17, line 325 – 336).

7. In the discussion on two side, woman should be changed into women. on page 12-13.

Author’s: We've corrected English grammatical errors.

8. You should say 'the main findings of the our study' rather than the following results in the first paragraph of discussion.

Author’s: We've corrected the sentence in the discussion section.

9. I think on page 17 line 361-263 should be removed from limitations. You assessed people from three regions it is not limitation.

Author’s: We have excluded the sentence from the discussion section.

10. On page 18 line 378 you should add years after 20-80.

Author’s: Thank you the note. We've supplemented the information in the conclusions section.

REVIEWER 2

Comments to the Author

Thank you very much for inviting me to review this original investigation about new reference equations for maximal respiratory pressures (MRP) and maximal voluntary ventilation (MVV) in Brazilian population. Even when several reference equations for MRP exist worldly and specifically in Brazilian adult population, I do believe this paper add value to the existing literature. Congratulation to the research team for the titanic effort done. However, some minor and also some major concerns should be answered by the authors.

Author’s: We appreciate your contributions and have carefully reviewed our manuscript, addressing each of your points. We believe it is now ready for publication.

Introduction

1. First paragraph (lines 51-54): I think references can be reduced in this paragraph.

Author’s: Thank you for your note. We removed the reference Rocha et al. (2007), by repeating information.

2. Lines 59-60: “While the validity of MVV during a 12 or 15-second test of such brief duration is uncertain in reflecting respiratory endurance”. I think the reference 6 (Laveneziana et al., 2019) should be included here. Indeed, the MVV is not recommended anymore by the ERS as an endurance test. That is why I think authors needs to reinforce the potential value of this new reference equations for MVV, both in the introduction and the discussion.

Author’s: Thank you for your comment. We've supplemented the reference, and we additionally complemented the information in the introduction section:

“Respiratory muscle endurance is assessed using maximal voluntary ventilation (MVV).[5] The validity of MVV in assessing respiratory endurance during brief 12 or 15-second test is uncertain.[6] Nevertheless, this maneuver assesses maximum ventilatory capacity, reflecting the functioning of the inspiratory pump and chest wall.[7] It is widely utilized clinically to determine ventilatory reserve,[8, 9] assess risk of postoperative complications[10] and establish targets for muscle training.[11]” (page 3, line 57-63).

7. Colwell KL, Bhatia R. Calculated versus Measured MVV-Surrogate Marker of Ventilatory Capacity in Pediatric CPET. Med Sci Sports Exerc. 2017 Oct;49(10):1987-1992. doi: 10.1249/ MSS.0000000000001318. Erratum in: Med Sci Sports Exerc. 2018 Feb;50(2):390. doi: 10.1249/ MSS.0000000000001521. PMID: 28489684.

8. American Thoracic Society; American College of Chest Physicians. ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2003 Jan 15;167(2):211-77. doi: 10.1164/rccm.167.2.211. Erratum in: Am J Respir Crit Care Med. 2003 May 15;1451-2. PMID: 12524257.

9. Arena R, Sietsema KE. Cardiopulmonary exercise testing in the clinical evaluation of patients with heart and lung disease. Circulation. 2011 Feb 15;123(6):668-80. doi: 10.1161/CIRCULATION AHA.109.914788. PMID: 21321183.

10. Bevacqua BK. Pre-operative pulmonary evaluation in the patient with suspected respiratory disease. Indian J Anaesth. 2015 Sep;59(9):542-9. doi: 10.4103/0019-5049.165854. PMID: 26556912; PMCID: PMC4613400.

11. Markov G, Spengler CM, Knöpfli-Lenzin C, Stuessi C, Boutellier U. Respiratory muscle training increases cycling endurance without affecting cardiovascular responses to exercise. Eur J Appl Physiol. 2001 Aug;85(3-4):233-9. doi: 10.1007/s004210100450. PMID: 11560075.

3. Lines 66-68: “Although previous studies suggested prediction equations for MIP, MEP, and MVV in the Brazilian population, [6, 9, 12-14]” I think reference number 6 is not adequate here. On the other hand, there are more reference equations for MIP and MEP in Brazilian population (i.e.: Sgariboldi et al. (2015) and Sánchez et al., (2018)). I suggest to include them in the introduction and use then after in the discussion to enrich the discussion. I miss reference equations for MVV in Brazilian population in this paragraph.

Author’s: Thank you for the note. We have excluded the reference in the introduction section. We do not included reference from Sánchez et al., (2018) and Sgariboldi et al. (2015), because this article focus on reference values for obese subjects. Regarding study of Sgariboldi et al. (2015), 76% of the subjects were include on overweight, obese or morbidity obesity.

4. Lines 76-78: MIP, MEP and MVV were already expanded above, you don´t need to expand the abbreviations again here.

Author’s: We've corrected the sentence in the introduction section.

5. There is an error concept along the manuscript between “gender” and “sex”. Authors mean sex (as a biological variable) and not gender (which is a social identification). Please, correct this error along the manuscript. According to the lasted statement from ERS for pulmonary function sex and gender should not be confounded in reference equations. https://doi.org/ 10.1183/13993003.01499-2021.

Author’s: We've corrected the sentence along the manuscript.

Methods

1. Firstly, is surprising that data were collected between 2009-11 and not published yet. How authors can explain this fact? If we take into account what ERS says about the obsolescence of reference equations (10 years- Eur Respir

J. 2005;26(5):948-68) these data are already obsoleted. How authors can defend these values as representative of the actual population?

Author: Thank you for your comment. In fact, the period during which data acquisition occurred was extensive. We experienced a delay in obtaining the analysis of the results because it was carried out across multiple centers and involved several collaborators. This is a limitation of the study, a point that will be emphasized in the discussion section. However, we believe in the potential for publishing our results, primarily due to the scarcity of studies in this field during the current period and the rigorous methodology with which the study was conducted. We additionally complemented the information in the conclusion section:

“Furthermore, it is imperative to highlight the previous period during which data collection occurred, as there was a delay in analyzing the results, which could potentially affect the relevance of the proposed equations.” (page 19, line 394-396).

2. Which was the strategy used for recruitment; where they obtain the sample; the strategy was the same in each research center?

Author’s: We have added a methods section - please see below:

“Participants were recruited by convenience through publicity to university students at each center, as well as via social media.” (page 5, line 98 and 99)

3. Which strategies were used to ensure the consistence of the measurements (did evaluators have some training, some quality control was performed, etc.)?

Author: All evaluators underwent prior training to ensure the reproducibility of the study and familiarize themselves with the materials and methods. Finally, the databases were populated, and a joint analysis of the results was conducted. For clarity, we have included the following information in the Methods section: "The same previously trained evaluator at each research center conducted both stages on the same day." (page 6, line 125 and 126).

4. Line 143: “acceptable when measurements varied less than 5% or were equivalent to 200 mL” [19]. In reference 19 (Graham et al 2019) authors state: “FVC repeatability is achieved when the difference between the largest and the next largest FVC is <0.150 L for patients older than 6 years of age (86) and

<0.100 L or 10% of largest FVC, whichever is greater, for those aged 6 years or younger (8, 87). For FEV1 repeatability, the difference between the largest and the next largest FEV1 is <0.150 L for those older than 6 years of age and <0.100

L or 10% of the largest FEV1, whichever is greater, for those aged 6 years or younger” Please, change the reference or change the numbers.

Author’s: Thank you for your considerations. We've corrected the sentence in the results section: "The assessment was repeated three to five times after one-minute intervals and considered acceptable when the difference between the two largest FVC and FEV1 values varied less than ≤0.150 L." (page 7, line 148 and 149).

5. Line 143-147: how many breaths per minute were aimed for the MVV? In reference number 20 (Miller et al., 2005) 90-110 bpm are remarked as ideal.

Author’s: The equipment used follows the technically accepted maneuver according to the ERS/ATS guidelines, the best, traces, were selected automatically based on this criterion. The breathing frequency is approximately 90 breaths per minute, following the reference of Miller MR, Pincock AC. Linearity and temperature control of the Fleisch pneumotachograph. J Appl Physiol 1986;60:710–715.

6. Lines 149-158: more technical details are needed. For example: which kind of mouthpiece were used; which pressure was used (peak pressure or plateau pressure- I know that MicroRPM measures the plateau but it should be clarified in the paper); was PUMA software used to see the graphs during the measurements; which quality criteria was used regarding the graph shapes; how much each maneuver lasted?; did the participants rest between maneuvers, and between MIP and MEP?; in which order subjects performed the tests (MIP, MEP and MVV), was always the same?

Author’s: Thank you for the note. We have added a methods section - please see below:

Study design “The order of respiratory assessments was randomized, respecting the 20- minute interval between them.” (page 6, line 123 - 125)

Respiratory muscle strength “The PUMA PC software (Micro Medical, Rochester Kent, UK) operationalized the MIP and MEP (equivalent to respiratory muscle strength) variables using the aforementioned maximum mean pressures. Participants performed a maximum inspiration from residual volume for MIP and a maximum expiration from total lung capacity for MEP, performing 3 - 5 maneuvers, with a 1 minute break between them. Both were assessed with participants using a disposable flanged mouthpiece and a nose clip.” (page 7, line 159 - 165)

7. Lines 160-169: Baecke HPA questionnaire was created for adults over 60 years old, but here it was applied for subjects from 20 years old. Did the

authors verify the psychometric proprieties of this questionnaire in the youngest? Could you add some reference?

Author’s: Thank you for your considerations. The reference cited in the methodology, Florindo and Latorre (2003), provides validation and reproducibility of Baecke's questionnaire for the Brazilian adult population. In their study, these authors evaluated a population with an average age of 32.6 ± 3.2 years. To assess the validation of the Baecke HPA questionnaire, they measured maximum oxygen consumption (VO2 max), percent decrease in heart rate (%DHR) using the Cooper 12-minute walk or run test, annual physical exercise index (IPE), and weekly locomotion activity index (ILA). They verified reliability through test-retest with a 45- day interval. The authors concluded that Baecke's HPA questionnaire is valid and reliable for measuring habitual physical.

8. Line 168 (about algorithm for interpretation) needs a reference. Author’s: Thank you for your comment. We've supplemented the reference. Results

1. Line 194: the sample size calculation was 366 subjects but the final sample is composed by 243 for MRP and 211 for MVV. How authors explain so the power calculation of this reference equations if they not achieve the sample size?

Author’s: The initial sample size was 183 participants. To mitigate potential data acquisition errors, we increased the sample size to a final total of 366 participants. We evaluated 243 subjects, which falls within the predefined range for our study.

2. Please review table 1: the HPA is under the anthropometric data and this is not correct. Moreover, it is highly important to add the number of subjects (n) achieved in each age group (add this information in the table); only them we can have an idea of the representation in each decade.

Author’s: We have edited the table 1 in the results section and added the sample size (n) to each age group. Regarding the HPA, we have retained it, as it was used as an inclusion criterion and for sample characterization.

3. I would suggest to merge the pulmonary function data with table 1, after all, these data were collected for characterized the sample, right?

Author’s: While your point about it being a characterization variable is valid, we opted to present the anthropometric and pulmonary function data in separate tables. This decision stems from the fact that our spirometric analysis predictive equation is already age-adjusted, making decade-by-decade analysis unnecessary

4. Lines 231-245: authors give p value of their new reference values compared with other reference values published in Brazilian population, but I don’t see this nor as an objective of the study or in the data analysis. Please, add this first as a secondary aim and in the data analysis.

Author’s: We've supplemented the information in introduction section - please see below: “In addition, we will compare the values resulting from our generated equation with those

Attachment

Submitted filename: Response to review.pdf

pone.0313209.s004.pdf (354KB, pdf)

Decision Letter 1

Ming-Ching Lee

22 Oct 2024

REFERENCE VALUES FOR RESPIRATORY MUSCLE STRENGTH AND MAXIMAL VOLUNTARY VENTILATION IN THE BRAZILIAN ADULT POPULATION: A MULTICENTRIC STUDY

PONE-D-24-16298R1

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thank you very much for your effort. All my concerns were adressed now. The article will be useful for interpretation of data in brazilian population

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Acceptance letter

Ming-Ching Lee

11 Nov 2024

PONE-D-24-16298R1

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Associated Data

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    Supplementary Materials

    S1 Table. Description of prediction equations for MRP and MVV from previous studies.

    (DOCX)

    pone.0313209.s001.docx (29.4KB, docx)
    S1 Data

    (XLSX)

    pone.0313209.s002.xlsx (27.6KB, xlsx)
    Attachment

    Submitted filename: Response to Reviewers.pdf

    pone.0313209.s003.pdf (33.6KB, pdf)
    Attachment

    Submitted filename: Response to review.pdf

    pone.0313209.s004.pdf (354KB, pdf)

    Data Availability Statement

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