The protocol and consent for this cross-sectional study were approved by the Institutional Ethics Committee. The study period was from October 7, 2014, to January 15, 2018. The institutions approached to recruit participants included 57 private and 37 public schools that attend to DS populations and care for disabled people (Multiple Care or Integral Development of the Family Centers, DIF-Mexico). The parents and guardians of the children, teenagers and adult participants were also invited to participate, regardless of the level of disability, comorbidities or genetic mechanisms (mosaicism, translocation or trisomy 21) involved in the DS cases. Recruitment involved visiting the aforementioned centers and speaking with institutional authorities, parents and guardians. A total of 302 participants aged 5–55 years, all residing at 2240m above sea level were included. The participants’ parents or guardians signed their informed consent. All PFTs were performed at a third-level referral hospital that attends exclusively respiratory diseases and uninsured patients.

Two trained nutritionists applied a questionnaire, took anthropometric measurements and performed nutritional assessments. All PFTs were supervised by the same experienced technician, who had trained for 6 months in a Respiratory Physiology Laboratory that has ISO-9001-2015 certification (International Organization for Standardization).

• 1)

  Anthropometrics: we measured height, weight and the body mass index (BMI) using an electronic scale with a body composition monitor (model HBF-500INT; OMRON, USA) and a portable stadiometer (model 213; SECA, USA).

• 2)

  Oxygen saturation (SpO2) and heart rate (HR) were estimated by a pulsioximeter, which also provided data on exhaled carbon dioxide (PetCO2) and respiratory rate (RR) (capnograph and LifeSense model LS1-9R oximeter, Nonin Medical). The pulsioximeter was placed on the right index finger to obtain six readings in 1min (i.e., every 10s). Averages are reported. Acceptable measurements for PetCO2 and RR were considered when the participant performed stable breathing at tidal volume. In this case, as well, the average of six measurements is reported.

• 3)

  IOS was performed by all participants (MSIOS; Erich Jaeger, CareFusion, San Diego, CA, USA), following recommendations published by several authors.5 Volume at three different flows (<2, 4–6, and >8L/s) and pressure calibrations of the equipment were verified daily using a certified 3-L syringe (maximum variability 3%) at a pressure of 0.2kPa (±0.01kPa).

In addition, linearity at three different flows (<2, 4–6, and >8L/s) was corroborated on a weekly basis. Briefly, with the subject in a sitting position and wearing a nose clip, the procedure was explained in plain language and she/he was allowed to become accustomed to the equipment. IOS measurements were taken during quiet tidal breathing with the subject's cheeks supported by a research assistant. All trials lasted 20s and were performed at 1-min intervals. To evaluate the acceptability of these tests, we focused on resistance at 5Hz (Rrs5) and applied the criteria described by Beydon et al.6 to classify them as acceptable or not. Good repeatability was considered if the intra-test coefficient of variation (CV) was <10%.

Spirometry and DLCO were performed according to American Thoracic Society/European Respiratory Society (ATS/ERS) 2005 standards.7

• 4)

  Forced spirometry was performed using the same equipment as IOS, with a maximum of eight forced expiratory maneuvers, of which three acceptable ones were selected, aiming for a difference ≤0.15L between the two highest forced expiratory volumes in 1s (FEV1) and forced vital capacities (FVC).

• 5)

  For the DLCO test (NDD EasyOne PRO), a minimum of two acceptable maneuvers that differed by ≤3mL/min/mmHg were required. The participants selected to perform this test were those who were able to inhale deeply up to total lung capacity and then exhale completely to residual volume.

• 6)

  The 6MWT was performed on a hard, flat surface in an interior corridor 40 meters long, following international standards.8 Only one walk was performed because of the long time required to run all the tests. The explanation and instructions for this test were visual and brief so that participants could understand them clearly. During this test, pulse oximetry and blood pressure were measured (standing baumanometer with movable base; Riester, Germany). Individuals were excluded if their SpO2 <90%, if they had uncontrolled heart disease or difficulty in walking, or if they did not understand the instructions, or refused to participate.

In order to evaluate variability among the different PFTs, the CV was calculated for each test. Medians (25th, 75th percentiles) were used to describe the data. Mann–Whitney and Wilcoxon tests were applied to compare medians. STATA ver.12 statistical software (Stata Corp., College Station, TX, USA) was used for all analyses.

A total of 302 children, teenagers and adults with DS were recruited; 51% were males. Median age was 18 years (12, 27) for males and 21 years (13, 26) for females. Table 1 presents the anthropometric measurements of all participants. Greater overweightness was found for females (BMI=28.7).

Table 2 shows the median of the main variables of each PFT by gender. Results show that 98% of participants were able to perform at least three IOS maneuvers without artifacts, and that 71% of all tests had adequate acceptability and repeatability (i.e., variability between measurements <10%) with resistance at 5Hz. Over 50% of participants in each age group reached the repeatability criteria. The 19–29 age group achieved the highest proportion of repeatable tests (79%, Table 3). Resistance at 5Hz had the highest percentage of repeatable tests (CV<10%) in the 19–29 age group (97%, Fig. 1).

Fig. 1.

Proportion of participants with a coefficient of variation <10% by PFTs and age group. *Considering the three best test.

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Forced spirometry was performed by 82% of participants, but most results (84%) were of poor quality (grade F with unacceptable maneuvers). In fact, the 19–29 age group achieved only 10% grade A or B quality (to fulfill the ATS quality criteria), mainly due to early termination or expiration cut-off, but also as a result of an obstructed mouthpiece, glottic closure or sub-maximal effort (Table 3). The 5–11 and 12–18 age groups had the highest proportions of poor quality tests (grade F).

Fig. 2 shows the median forced expiratory time (FET) by age group. In all cases, this measurement was less than 2s, though it tended to increase with age, only 1.6% of participants managed to blow ≥6s [median 1.5s (1.17, 2.13) (Table 3).

Fig. 2.

Comparison of median FET by age group.

*Wilcoxon tests.

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Despite these findings, we went on to evaluate the repeatability (<0.150L of the two largest values) of FEV1 and FVC, which were performed by 83% of the 19–29-year-olds for FVC, and 61% of the 30–55-year-olds for FEV1 (Table 3).

The DLCO test was performed by 128 (42%) individuals, but it was not possible to evaluate the existing acceptability criteria because of uncertain, likely underestimated, vital capacity due to short expirations. However, the DLCO results of most participants were within normal limits (Table 2). In this case, 39% of participants reached a DLCO ≥80% of predicted according to Mexican reference values.9 Only 26% of 19–29 age group achieved an inspiratory volume >85% of FVC; results were lower for the other age groups (Table 3). Similarly, the proportion of participants with a CV <10% was the lowest index determined in all age groups (Fig. 1). However, the apnea time of 10±2s and the expiratory time <3s were accomplished by almost all participants in each age group.

Most participants (75%) performed the 6MWT, but 13 stopped before 6min, and 4 tests were canceled because of dyspnea. The 6MWT was not performed by 75 participants for the following reasons: 54 refused; 13 had oxygen desaturation at rest (≤90%); and 8 were unable to walk. Table 2 describes the median (p25, p75) number of meters walked by the participants who completed the test. A statistically-significant increase in heart rate was observed after 6MWT, even though participants did not make maximum effort, according to the technicians’ reports.

Although capnography variables (Table 1) do not require much collaboration on the part of patients, the proportion of participants with a breathing frequency CV<10% was very small (Fig. 3), whereas 65% in the 5–11 age group achieved repeatable PetCO2. Measurements of SpO2 and HR were acceptable in almost all participants.

Fig. 3.

Proportion of participants with a coefficient of variation <10% for capnography variables by age group.

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Our participants were unable to perform all the components of this respiratory function test battery, but evaluating feasibility was, precisely, one of the main objectives of the study. We did not measure participants’ cognitive levels prior to performing the PFTs as a possible predictor of the inability to perform them.17 Finally, it is probable that we included participants with cardiac diseases and other undiagnosed comorbidities, which are very common in this population and could affect test performance and results.