Assessment of airflow limitation in patients with obstructive sleep apnea

Background Obstructive sleep apnea (OSA) is a prevalent sleep breathing disorder affecting 9–25% of the general adult population. Aim To assess airflow limitation by spirometric indices in patients with obstructive sleep apnea. Patients and methods This observational case–control study was conducted on 60 subjects who were divided into four groups: Group I (control group), included 20 subjects chosen from other departments, who had no respira‑ tory complaints with apnea–hypopnea index (AHI < 5); Group II (mild group), included 11 patients with mild sleep apnea, 5 ≤ AHI < 15; Group III (moderate group), included 17 patients with moderate sleep apnea, 15 ≤ AHI < 30; and Group IV (severe group), included 12 patients with severe sleep apnea, AHI ≥ 30 at the Chest Department, Faculty of Medicine, Helwan University, from August 2021 until June 2022. Results There was no statistically significant relation found between the severity of AHI and all the previous pul‑ monary function parameters except a statistically significant decrease in FEF (25–75%) in the moderate group than the mild group and also in the severe group than the moderate group ( p ‑value < 0.001). There was a statistically significant positive correlation found between AHI and BMI and NC and a negative correlation found between AHI and FEF (25–75%) while no statistically significant correlation was found between AHI and the other studied parameters. Conclusion Obstructive sleep apnea (OSA) is associated with airflow limitation by spirometric indices, although this association is statistically insignificant. On the other hand, the severity of obstructive sleep apnea is directly propor‑ tional to the seriousness of the apnea–hypopnea index (AHI). Strong correlations were found between the severity of AHI and body mass index (BMI), neck circumference, and FEF (25–75%).


Introduction
Obstructive sleep apnea (OSA) is a prevalent sleep breathing disorder affecting 9-25% of the general adult population [1].Frequent partial (hypopnea) or complete (apnea) closure of the upper airway during sleep leads to oxygen desaturation, increased respiratory effort, arousal, and sleep fragmentation.Patients typically present with witnessed apneas, loud intermittent snoring, and excessive daytime somnolence [2].The syndrome is associated with impairment in quality of life, cognitive function, and work performance [3].
OSA is considered an important health problem and is associated with complications such as hypertension, ischemic heart disease, pulmonary hypertension, cardiac arrhythmias, stroke, and sudden death [4].
Patients with OSA have various structural and functional abnormalities of the upper airway during sleep, which may reflect on their pulmonary function tests [5].The obstruction in breathing due to the narrowing of the upper airway causes a marked increase in intrathoracic pressure and triggers apnea and hypoxia [6].
Spirometry and flow-volume loop are simple and commonly used tests in patients with respiratory symptoms.Several screening questionnaires and clinical screening models have been developed to help identify patients with OSA [7].
Polysomnography studies are an essential tool for the sleep physician and aid in the diagnosis and treatment of sleep disorders [8].
This study aimed to assess airflow limitation by spirometric indices in patients with obstructive sleep apnea.

Patients and methods
This observational case-control study was conducted on 60 subjects who were divided into four groups according to their apnea-hypopnea index: Group I (control group), included 20 subjects chosen from other departments, who had no respiratory complaints with apnea-hypopnea index (AHI < 5); Group II (mild group), included 11 patients with mild sleep apnea, 5 ≤ AHI < 15; Group III (moderate group), included 17 patients with moderate sleep apnea, 15 ≤ AHI < 30; and Group IV (severe group), included 12 patients with severe sleep apnea, AHI ≥ 30 at the Chest Department Faculty of Medicine, Helwan University, from August 2021 until June 2022.
Inclusion criteria: Patients > 18 years, both genders, and patients diagnosed with OSA by polysomnography.
Exclusion criteria: Patients below 18 years, patients who were unable to perform spirometry, and patients with other chronic respiratory illnesses, e.g., inflammatory lung diseases (ILD).

Methods
All candidates were subjected to full history taking, including smoking history (age of initiation, duration of exposure, number of cigarettes smoked, stop exposure or not), full clinical assessment, and radiological examination.

Spirometry pre-and post-bronchodilator
Dynamic spirometry was performed using the MIR Spirobank II Spirometer (MIR Medical International Research, MIR ITALY Headquarters: Via del Maggiolino 125 00155 Roma).The test was done before and after giving a nebulizer of 5 mg of salbutamol sulfate with 2 ml saline 0.9% for 3 min, we also measured FEF/FIF50 and saw tooth appearance to find out the pharyngeal narrowing and collapsibility.

Technique
Calibration was done before measurement.Nose clips were inserted.Using the mouthpiece, tidal (normal) breaths can be taken first, then a full deep breath taken in, performing the forced full expiration (empty their lungs in 6 s), followed by a further quick, full inspiration.
Encouragement makes a big difference, so raise your voice to encourage the patient, particularly near the end of the maneuver [9].

Polysomnography (PSG)
This was done in the Pulmonary function laboratory, Using a MINISCREEN PRO polysomnograph recorder (LOWEINSTEIN).The MINISCREEN PRO is a portable multichannel polysomnography recorder that records physiological activity data on a flash memory card or PC.It can record up to 27 channels, depending on the hardware configuration and flashcard used.The lightweight system is comfortable for patients and clinicians, allowing them to sleep and move freely while recording.Patients can prepare for recording sessions by attaching sensors, setting up and configuring the device, and ensuring sensor information is gathered properly.The recorded patient data can be retrieved.

Standard equipment
The MINISCREEN PRO system consists of the following standard equipment: Carrying case, recorder, battery recharger, AC/DC, power supply (for battery recharger), EZRig porterage system (includes patient-vest and recorder pouch) MINISCREEN PRO sensors with corresponding cables, at least one of the following headboxes: Fast-wave headbox and slow-wave headbox.Each component of the MINISCREEN PRO system connects directly or indirectly to the recorder.The recorder data is on a flash memory card that is inserted into the flash card slot.It is also possible to record on a PC using the lastest software version, in this case, MINISCREEN collects the data and transfers them to the computer where they are stored on the hard disk.A built-in battery pack powers the recorder and can be recharged using the battery recharger.There is a dedicated part for the setup and configuration unit and battery recharger.

Arrangement in the sleep laboratory
Before scheduled testing, patients are advised to shower, wash their hair, remove makeup, nail polish, and body lotions, and avoid facial hair.Sensor placement works best in areas without facial hair, so braided hair needs to be upbraided.The patient should have eaten their last meal of the day to prevent damage to the thermistor and avoid tranquilizers, sedatives, or caffeine.

Nasal/oral airflow sensor (Thermistor)
The Nasal/Oral airflow sensor is a flexible, adjustable mustache-type sensor with three thermistors that can be positioned on the patient's face, adjusting to their facial contours.The sensor is flexible and adjustable, allowing for a comfortable and secure fit.It is inserted into the nasal/oral airflow sensor connector on the headbox and can be further secured using tape.

SPO 2 and heart rate sensor (pulse oximeter)
The SPO2 and heart rate sensor (pulse oximeter) is a device that measures blood pressure and heart rate by detecting changes in blood pressure.It is attached to the fingertip, with the receiver section aligned with the fingernail.Before placing the sensor, remove any fingernail polish.If using a tape sensor, wrap a flexible tap around the finger without restricting blood flow.If using a clip sensor, clip the sensor to the finger and fix the wire to the wrist, leaving extra length to prevent movement.

Results
There was no statistically significant difference between the group I and patient subgroups regarding age and sex (p-value = 0.619 and 0.224), respectively.While there was a highly statistically significant difference between BMI and NC (Table 1).
There was a highly statistically significant difference between the normal group and patients' subgroups regarding FEV1%, FVC, and FEF (25-75%) and a statistically significant difference regarding FEV1/FVC (Table 2).
There was no statistically significant difference between the studied patients regarding age, sex, weight, and height while there was a highly statistically significant difference regarding BMI and NC (Table 3).
There was no statistically significant relation found between the severity of AHI and all the previous pulmonary function parameters except a statistically significant decrease in FEF (25-75%) in the moderate group than the mild group and also in the severe group than the moderate group with p-value < 0.001 (Table 4).
There was no statistically significant relation found between the severity of AHI and all the previous PSG parameters (Table 5).There was a statistically significant positive correlation found between AHI and BMI and also NC of the studied patients and also a negative correlation found between AHI and FEF (25-75%) while no statistically significant correlation was found between AHI and the other studied parameters (Table 6).

Discussion
As part of the current study, we found that: airflow obstruction is typically classified as possibly flow limited when the flow: drive ratio falls below 86%, that is when the drive rises by one-sixth without an increased airflow.
While this derangement may sound minimal, we note that this threshold is similar to a 2-cmH2O increase in esophageal pressure swings from a 10-cmH2O baseline, double the 1 cmH2O threshold used previously [10], visual inspection of traces in this class reveals clear flow abnormalities.Airflow obstruction is scored as certainly flow limited (v.possible or normal) when the flow: drive ratio falls below a 58% threshold.Thus, periods of certain flow limitation may be interpreted to exhibit at least doubled respiratory drive/effort levels (note drive rises with obstruction more than flow falls, due to chemoreflex compensation [11].The flow limitation frequency was  only modestly associated with disease severity as measured by the AHI, in our study of patients with diagnosed OSA.Notably, participants referred for evaluation of OSA without moderate-severe OSA in our study exhibited flow limitation (certain + possible) for a clinically meaningful duration (> 30% of total sleep time; per prior definition of upper airway resistance syndrome [12]: some of these participants exhibited certain flow limitation for over 30% of total sleep time.On the other hand, about a few OSA patients did not have certain flow limitations for over 30% of total sleep time.Thus, higher AHI does not necessarily indicate increased flow limitation frequency (or greater risk of any flow-limitation-specific sequelae).These results correspond with data from literature and demonstrate that-in patients with OSA-flow limitation (certain or possible) is surprisingly prevalent (81 (36-100)% of breaths, mean (range)), and is also common during arousals (40 (5-85)%) and stable breathing (58 (12-91)%), with a wide variety across patients.These data demonstrate that some (but not all) participants exhibit substantial flow limitation during their arousal-related recovery periods; notably, failure to fully recover between events is associated with adverse outcomes [13] and may be a distinct phenotype.Some participants exhibit substantial flow limitation during stable breathing periods, that is, when breathing is conventionally assumed to no longer require medical intervention, while others appear to achieve stable breathing with minimal flow limitation.It is now possible to examine the implications for sleep apnea sequelae through further investigation.
Currently, there is a major clinical need for a non-invasive automated method to quantify the frequency of flowlimitation (airflow obstruction) to detect obstructive sleep-disordered breathing in patients without overt OSA, as well as for providing insight into OSA phenotypes (e.g., higher vs. lower ventilatory drive/effort).It is understood that both the symptoms and sequelae of sleep-disordered breathing are not fully captured by the frequency of respiratory events (AHI) [14].In particular, numerous symptomatic individuals exhibit unrecognized flow limitation for a substantial proportion of the night [15] and may benefit from treatment [16].The corollary is that many patients currently diagnosed (using AHI) may not have a phenotype of sleep-disordered breathing that has a major impact on daytime function or outcomes.A large body of accumulated evidence now points to an independent role for flow limitation in the adverse outcomes of pharyngeal obstruction, independent of event frequency.Measures of flow limitation have been associated with hypertension and sleepiness independent of the AHI [17].Surgical treatment to address flow limitation in children and adults has been effective at relieving symptoms [18].CPAP treatment of flow limitation in pregnancy can improve preeclampsia [19].
The data shows that there was a statistically significant increase in BMI and NC in moderate and severe AHI groups than normal group and mild group with p-value < 0.001 and < 0.001; respectively.Also, the percentage of obese patients was found significantly increased in AHI subgroups than the normal group with a p-value < 0.001.this corresponds with previous studies like Jehan et al., which conclude that Obese people must be screened for OSA and disorders that are associated with it.Both obesity and OSA patients have a greater risk of metabolic syndrome [20].

Limitations
The study had several limitations, including a relatively small sample size, the need for reasonable quality airflow signals, and the broad definition of flow limitation used to describe pharyngeal airflow obstruction.The study also found that it does not apply to excessively smoothed, distorted, clipped, or noisy data.Additionally, the study's broad definition of flow limitation, including non-rounded airflow shapes like flattening, scooping, jaggedness, and fluttering, necessitated the development of a new method based on flatness.

Conclusion
Obstructive sleep apnea (OSA) is associated with airflow limitation by spirometric indices, although this association is statistically insignificant.On the other hand, the severity of obstructive sleep apnea is directly proportional to the seriousness of the apnea-hypopnea index (AHI).Strong correlations were found between the severity of AHI and body mass index (BMI), neck circumference, and FEF (25-75%).

Table 1
Comparison between the group I and patient subgroups regarding demographic data and characteristics of the studied patients NS non-significant, P-value > 0.05, S significant, P-value < 0.05, HS highly significant, P-value < 0.01, NC neck circumference

Table 2
Comparison between normal group and patients' subgroups regarding pulmonary function parameters NS non-significant, P-value > 0.05, S significant, P-value < 0.05, HS highly significant, P-value < 0.01

Table 3
Relation of AHI severity with demographic data and characteristics of the studied patients NS non-significant, P-value > 0.05, S significant, P-value < 0.05, HS highly significant, P-value < 0.01

Table 4
Relation between AHI severity and pulmonary function parameters of the studied patients NS non-significant, P-value > 0.05, S significant, P-value < 0.05, HS highly significant, P-value < 0.01; •one-way ANOVA test; ‡Kruskal-Wallis test

Table 5
Relation between AHI severity and distribution of PSG parameters of the studied patients NS non-significant, P-value > 0.05, S significant, P-value < 0.05, HS highly significant, P-value < 0.01; •one-way ANOVA test; ≠ Kruskal-Walli's test

Table 6
Correlation of AHI with age, anthropometric measures, and pulmonary function parameters of the studied patientsData in bold refere to the significant data