Aerossolterapia em indivíduos obesos com ou sem DPOC: análise do padrão de deposição pulmonar e determinação de fatores preditores
Introduction: Obesity is responsible for triggering several systemic alterations, increasing the severity and morbidity of existing pathologies. Obese individuals with respiratory diseases, such as chronic obstructive pulmonary disease (COPD), have higher rates of dyspnea, worse overall health, h...
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| Formato: | doctoralThesis |
| Idioma: | pt_BR |
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| Endereço do item: | https://repositorio.ufrn.br/jspui/handle/123456789/27382 |
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| Resumo: | Introduction: Obesity is responsible for triggering several systemic alterations,
increasing the severity and morbidity of existing pathologies. Obese individuals with
respiratory diseases, such as chronic obstructive pulmonary disease (COPD), have
higher rates of dyspnea, worse overall health, higher consumption of medications and a
lower effectiveness of inhaled medications compared to patients with normal weight.
Thus, it is important to understand which factors are responsible for the low
effectiveness inhaled medication in the obese population. In addition, the possibility of
implementing aerossoltherapy via a high-flow nasal cannula to improve the deposition
pattern in this population has not yet been described. Objectives:
Study 1- To analyze the association between anatomic variables of the upper airways of
healthy obese individuals and the percentage of pulmonary deposition of inhaled
radiopharmaceuticals. Find predictors for this deposition.
Study 2 - To analyze inhaled aerosol pulmonary deposition via High Flow Nasal
Cannula (HFNC) in patients with COPD (obese and non-obese)
Study 3 – To develop a realistic 3D printed oropharynx from a computed tomography of
a healthy adult volunteer and it on in vitro measurements. Methods: This research was subdivided into two distinct parts: in vivo and in vitro. The
first part was composed of two studies. The 1st Study was a non-randomized
controlled clinical trial with obese and non-obese individuals. The following were
evaluated: upper airway anatomical and anatomical characteristics (Computed
Tomography and modified Mallampati score). All volunteers inhaled
radiopharmaceutical (99mTc-DTPA; 1mci), with bronchodilator Fenoterol
hydrobromide and ipratropium bromide using membrane inhaler (MESH) during quiet
breathing (tidal volume). Deposition comparisons were performed between obese group
and the non-obese groups. Meanwhile, the 2
nd Study was a crossover trial where
patients with COPD inhaled radiopharmaceutical (99mTc-DTPA; 1mci), with
bronchodilator Fenoterol hydrobromide and ipratropium bromide on two different days
(at least two days apart). One day, inhalation occurred simply using membrane inhaler
(MESH), while in the other day the inhalation occurred via the CNAF. The sequence of the intervention was previously randomized. In turn, the Second part presents the
development of a 3D printed oropharynx (3DOR) from a healthy adult volunteer, based
on upper airways tomographic images during an inspiratory pause, with the mouth
opened. With the model, it was possible to evaluate the effects of the anatomic
characteristics over the aerosol inhalation using a Mesh nebulizer and how a Meshcamber could affect the inhaled dose. In an in vitro system, attached to a breath
simulator, a Mesh nebulizer was used to deliver Salbutamol Sulphate, with and without
a Mesh-chamber, through two distinct inlets: 3DOR and USP (United States
Pharmacopeia Inlet). As outcome measurements, we have considered the amount of
medication deposited in the 3DOR and USP, as well as in the filters (inspiratory and
expiratory), as a percentage of the total loaded dose in the Mesh nebulizer. Study results 1: Participated in the study 17 non-obese and 12 obese subjects. The
volunteers of the obese group had 30% lower pulmonary deposition than non-obese
patients (p = 0.01, 95% CI 0.51 to 4.91). Anatomical variables related to airway shape
differed between groups. The anteroposterior diameter of the obese retroglossal region
was 29% higher (p <0.01, 95% CI -5.44 to -1.1), while the lateral diameter was 42%
lower (p = 0.03, 95% CI % 0.58 to 11.48), compared to non-obese individuals. The
cross-sectional area of the retropalatar region and its relationship with the crosssectional area in the retroglossal region were also lower in obese (p <0.05). None of
these variables correlated with pulmonary deposition of the inhaled aerosol. Meanwhile,
BMI was responsible for 32% of the variance of pulmonary deposition (p <0.001; β -
0.28; 95% CI -0.43 to -0.11). When analyzed under the subdivision of modified
Mallampati grades, obese class 4 subjects had 44% less pulmonary deposition of
inhaled radiopharmaceuticals than non-obese subjects in the same classification. Conclusion of Study 1: The anatomical alterations of upper airways, due to obesity, seem to not interfere in pulmonary deposition more than BMI alone. However, obesity associated with modified Mallampati class 4 was responsible for an exacerbation of the difference in pulmonary deposition between obese and non-obese individuals, which
may be a detrimental factor to the offer of inhaled medication in the obese population.
Results of study 2: After the screening, 11 COPD patients participated in the study.
The control group presented a median percentage of pulmonary deposition of 2.8% (IQR 3), meanwhile, HFNC was 3.0% (IQR 1,3, p> 0.05; Mann-Whitney test). Despite
the similarity in the total lung deposition, the aerosol penetration index was significantly
higher in the HFNC group (1.38 IQR 0.37) than in the Control group (1.12 IR 0.34;
p=0.023)The deposition in the upper airways was higher with HFNC compared to the
control group (28% IQR 8, and 11% IQR 5, respectively, p = 0.01). Stratified analysis
based on BMI (i.e. obese and normal weight) did not show additional benefits to the
obese patients submitted to HFNC. Conclusion of Study 2: The high flow nasal cannula as an aerossoldelivery method
presented a similar pulmonary aerossoldeposition in COPD patients. Although, the
intervention allowed a higher peripheral aerosol lung deposition. Conversely to our
hypothesis, the positive pressure generated by the high flow device did not seem
improve the aerosol pulmonary deposition in the obese subjects. Results of Study 3: When the USP Inlet with VMc was used, the drug on EF was reduced from 48(7) to 6(1)%, and with the 3DOR, 52(10) to 14(2)%. The mass in the IF increased from 35(2) to 61(2)% and 26(3) to 43(2)% for USP and 3DOR respectively.
Losses in the USP were 2(0.6) and 3(1)% for VM and VMc, respectively. In contrast
12(4) and 22(4)% in 3DOR. T-test for the IF (USP vs 3DOR) showed a mean diff. of
18% (CI 95% 15-21). Conclusion of Study 3: The use of a mesh-chamber for inhalation procedure allowed a
large increase in the amount of medication collected in the inspiratory filter with both
inlets. Meanwhile, the expiratory filter percentage presented a significant reduction,
suggesting that the mesh-chamber acts as a reservoir during the exhalation promoting a
larger availability of aerosol during the inspiration. A lower deposition in the USP inlet
may, overestimated drug delivered distal to the inlet, indicating that inlet choice can
affect dose measurements. |
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