Lung Body Plethysmography: From Functional to Clinical Aspects for Prediction of Quality of Life in Patients with Chronic Pulmonary Obstruction

ROXANA MARIA NEMES1, FLORENTINA LIGIA FURTUNESCU2,*, IOAN SORIN TUDORACHE1, TUDOR HARSOVESCU1, ALEXANDRA FLORIANA NEMES2, MIRONELA PIRNAU3 1Titu Maiorescu University, Faculty of Medicine, 67A Gheorghe Petrascu Str, 031593, Bucharest, Romania 2Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd, 050474, Bucharest, Romania 3Titu Maiorescu, Faculty of Informatics, 189 Calea Vacaresti Str, 0400511, Bucharest Romania

COPD currently occupies sixth place on the list of causes of morbidity in the world in the adult population and tends to arrive in third place in the non-smoking 2030 [1]. The cost of the disease is very high [2,3].
Pulmonary functional tests are essential for diagnosis in patients with COPD. Spirometry is considered the most reproducible, and routine test in measuring airflow limitation. In COPD diagnosis relies mainly by highlighting the obstruction using FEV 1 [2,4].
St. George's Respiratory Questionnaire (SGRQ) was developed by PW Jones et al. being the most commonly used questionnaire in assessing the quality of life in chronic respiratory diseases (bronchial asthma, COPD), particularly in COPD [5]. It includes 76 questions grouped into three areas: symptoms, activity, impact. True or false responses are subsequently converted into numerical scale, resulting in field-specific scores and overall scores, which thus allow statistical processing of patient-provided information. The values of these scores are in the range 0-100, where 0 quantifies perfect quality of life, and 100 a maximum impact on quality of life related to health. The questionnaire can be: self-administered or administered by interview, frequently being self-administered. The time required for administration is approximately 20 minutes. We used a self-administered questionnaire for our research.
During forced expiratory maneuvers, patients with COPD can assist in decreasing FEV 1 . This occurs with the severity of the disease. Increasing the effort produces a compression on the thorax gas (Boyle's law): pV = constant (p=pressure, V= volume), which leads to the reduction of the pulmonary volume and implicitly to the reduction of FEV 1 . This is all the more pronounced as the residual volume (RV) is higher (severe hyperinflation). HRQL is a global measure that integrates more biological effects, unlike spirometric variables (FEV1) that measure a single biological variable [6]. Starting from these premise, HRQL measurement is important for at least two reasons, somewhat related to each other: -assessing the impact of the disease on the patient's life, which is of much greater interest to it than the classical assessment of disease severity (FEV 1 ); -assessing the impact of the disease on the patient's life, which is of much greater interest to it than the classical assessment of disease severity (FEV 1 );
The recruitment of patients was carried out according to the following inclusion and exclusion criteria: Inclusion criteria: -clinical-functional diagnosis of COPD -history of smoker> 20 PA.Calculation no. packets-year (PA) according to the formula: x i = number of cigarettes smoked per day n i = period in years corresponding to x i -patient's inform consent of complex lung investigation and to use the data for the present research.
Exclusion criteria: diagnosis of bronchial asthma, the uncertainty of the diagnosis, lack of anamnestic data, the impossibility of performing complex lung investigations, exacerbation in the last 30 days before lung function tests [7,8].
Spirometry was performed using a flowscreen Jaeger daily calibrated and check the validation of each registration data. The parameters measured by spirometry were: vital capacity (VC), flow expiratory volume in one second of an expiratory forced manouver (FEV 1 ), ratio FEV 1 / VC, maximal expiratory flow at 50% of vital capacity (MEF50). The parameters values are express in liter (L) or percent of predicted value. We performed body plethysmography for measure TLC (total lung capacity), residual volume (RV), cuantify the level of hyperinflation. We expressed RV as percent of predicted value (VRP%).
The equipment used is a Masterscreen Jaeger body plethysmograph. It is a plethysmograph equipped with an automatic calibration system according to temperature and pressure in the environment. The transparent plethysmograph allows the contact with the patient to perform maneuver, both visually and vocally.
Bodypletysmography technique: we explains in details for the patient the maneuvers to be executed; the subject will sit in the body pletysmograph cabin and, after closing the cabin door, will wait for a minute to breathe quietly; then the patient is asked to breathe through the mouthpiece attached to a pneumotograph; from now on, the patient will have the nostrils until the maneuvers are over [9]. After some quiet breathing maneuvers the patient will deeply inhale against a shutter by a technician who interrupts very short the airflow to the mouth; then exhale and inhale until the complete maneuvers that allow for a spirometry after the rupture of the obstacle the patient will be carefully supervised for the very duration of the tests to achieve very good cooperation. The physician monitors throughout the entire sample of the sample and graphically plotted on the computer monitor and the alveolar volume-volume loop recording (Figure 1), where VR -residual volume, CIinspiratory capacity, VER -spare expiratory volume.
-the test χ2 (Chi square) and its variants (Yates corrected, Mantel-Haentszel, exact Fisher) for discrete variables (categorical, including dichotomous ones) -the Student (T) test: comparing 2 lots by comparing their averages for the same variable having a parametric distribution (normally distributed) -Mann-Whitney (U) test comparing more than 2 lots by comparing their averages for the same variable with nonparametric distribution -Anova test (A) comparing more than 2 batches by comparing their averages for the same variable with parametric distribution.

Results and discussions
211 patients were enrolled according to the inclusion criteria listed above. The study group has the following characteristics listed in Table 1. Parameters obtained allow the assessment of the central resistance to flow (Raw), residual volume (VR) and total pulmonary capacity, being the only method that allows the total determination of these pulmonary volumes. Ecocardiography was done to identify the elements of chronic cor pulmonare.
Analyzing the three groups of hyperinflation severity we identified that for group 1 (mild hyperinflation 130% ≤ VRP% < 180%) we have a total of 44 patients who consumed a total of 1545 PA, while patients in group 2 (moderate hyperinflation 180% ≤ VRP% < 240%) consumed a total of 3267PA, and the number of patients being analyzed was 81. It results that for the same time period analyzed, the number of patients doubled, whereas between the arithmetic mean of consumption of the packets of the two classes there was a the very small difference, its value being 4.05 (p> 0.001). Group 3 (severe hyperinflation VRP% ≥ 240%) contains 75 patients who together consumed the highest number of PA as shows in fig. 3.
Below are the regression equations obtained for the VRP% value depending on the four GOLD stages of the obstruction verticality. (Table 4). Those with severe ventilator dysfunction (GOLD 4) showed significantly higher pulmonary hyperinflation values than those in GOLD 1 (p = 0.007) as shown (Table 5).
Comparing the mean values and standard deviations of VRP% (see table 6) for subgroups of patients with different nutritional status (goups BMI 1,3,4) versus those with BMI group 2 (normoponderal) we found no significantly difference in underweight patients versus normoponderal patients (p = 0.27, A).
The first sign of the alarm is that 61.6% (130/211) of the subjects analyzed started to smoke before the age of 20 years (table 7). Also, 70% of overweight young people began to smoke before 20 years, and 13% of them had severe hyperinflation. (VRP%> 240% of predicted value).
The VRP% analysis with smoker status highlighted a large dispersion of PA values ( Figure 4) and a lack of linear correlation between PA and VRP% (R = 0.01, Pearson). The same high displacement of VRP% by PA was also   3 . A comparison of the minimum, maximum and average package distributions related with hyperinflation severity groups Table 4 REGRESSION EQUATIONS OF VRP% DEPENDING ON GOLD STAGING obtained for patients who were smokers at the time of the determinations ( Figure 5). The additional exposure to industrial chemicals, dust, gases or presence of comorbidities such as diabetes mellitus, hypertension, tuberculosis, pulmonary neoplasm, other neoplasms and infections may be risk factors correlated with the severity of hyperinflation [12][13][14][15][16][17].
By analyzing the additional exposure to noxius substances we found no contribution as risk factors for the  increase in residual volume in patients in the global group (Table 9 ).
Patients with chroniccor pulmonale have a higher risk to associate severe hyperinflation (table 10) than those who did not have chronic pulmonary heart disease (p =0.0001).
The analysis of the links between the scores of the quality of life questionnaire (tabel 10) for the 211 patients who received the questionnaire, found that there were no differences in the impact score (SGRQi), activity score (SGRQa), symptom (SGRQs) score and total scores (SGRQt) of the hyperinflation groups studied (see table  11).
Patients with severe hyperinflation (77.5%) had a significantly higher activity score (p = 0.04, A) than those with mild and moderate hyperinflation Dividing into two groups (men and women) and studying differences in smoking history allowed a significant difference to be noted between the two groups. These differences were related to the onset of smoking (F = 0.35; p <0.01) and the number of smoking-year packs: PA (F = .01). This shows for the studied group, a much earlier start of smoking in men than women, a higher quantum of smoked packets, and a different pulmonary function (p <0.01 for FEV 1 ) and indicates a much higher susceptibility of female gender to develop COPD at a much lower smoker history than male, confirmed information and literature data [18][19][20][21].
Comparing the mean values and standard deviations of VRP% for subgroups of patients with different nutritional status (4,3,1) versus those with BMI group 2 (normoponderal), we found a significantly higher value of   A). But there is a paradox of obesity in patients with COPD. While in the general population, obesity is associated with an increased risk of mortality, Celli et al [22] finds that overweight and obesity are associated with a lower risk of death in patients with COPD. Patients with severe hyperinflation had a significantly impact of quality of life activity score. They have a higher activity score (p = 0.04, A) than those with mild and moderate hyperinflation related because of decreasing the daily activities [23,24].
By analyzing the additional presence of noxious or other comorbidities (diabetes mellitus, hypertension, pulmonary neoplasm) on the severity of hyperinflation, we found no contribution as risk factors for increasing the residual volume in patients in the global group [25,26].
Smoking cessation remain an important opportunity in the treatment of patients with COPD to avoid severe functional impairment and reducing the quality of life [27,28].

Conclusions
The benefits of the approach to investigation (body plethysmography) for assessing and monitoring patients with COPD is very important. These will be taken into account in further investigation protocols because allows the calculation of pulmonary volumes, inaccessible to the routine spirometry method, essential parameters in the evaluation and long-term monitoring ofquality of life in patient with COPD, taking into account the limited information value of FEV1, performing a complete functional diagnosis for assessing the patient with COPD.
Only by calculating the residual volume can be found the value of the total pulmonary capacity and, implicitly, the correct assessment of the type of dysfunction, the pattern of patented obstructive ventilator dysfunction, the value of pulmonar y hyperinflation, essential in the preoperative assessment and calculation of air-trapping volume.