ORIGINAL ARTICLE Year : 2021  |  Volume : 70  |  Issue : 1  |  Page : 48-53

Changing the airway pH: is it helping asthma control?

Nasef Abd-Elsalam Rezk1, Ahmed Alshamy2, Mohamed Shehta1, Nesreen Elsyed Morsy1, Mohamed Alnahas3
1 Department of Chest Medicine, Faculty of Medicine, Mansoura University, Egypt
2 Department of Anesthesia, Faculty of Medicine, Mansoura University, Egypt
3 Clinical Pathology, Faculty of Medicine, Mansoura University, Egypt

Date of Submission06-Jul-2020Date of Decision27-Jul-2020Date of Acceptance04-Oct-2020Date of Web Publication27-Mar-2021

Correspondence Address:
MD Nasef Abd-Elsalam Rezk
Department of Chest Medicine, Faculty of Medicine, Mansoura University
Egypt

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ejcdt.ejcdt_98_20

Background Although airway hyperacidity may have a great effect in the pathogenesis of asthma, its evaluation may be difficult. This study was conducted at Mansoura University Hospitals aiming to evaluate the degree of asthma control by increasing pH in uncontrolled asthma cases by the use of inhaled NaHCO3 8.4% for 3 months.
Patients and methods A total of 100 patients with asthma were included, and they were divided by simple randomization to 75 patients in study group and 25 controls. All participants were subjected to history taking, clinical examination, sputum cell count and pH assessment, PFT, high-resolution computed tomography, and sputum induction and NaHCO3 8.4% inhalation. Evaluation of asthma exacerbation 6 months before and after intervention was carried out.
Results There was no significant difference between study and control groups regarding demographic data, all basic investigations, pulmonary function, or sputum total and differential cells. We found a significant increase of sputum pH after treatment in the study group. Furthermore, significant improvement of forced expiratory volume in 1 s, forced vital capacity, four parameters of control assessment, and exacerbation also was seen in the study group after treatment. There was a significant decrease of total cells and eosinophils in sputum in the study group. The linear regression model showed a significant negative correlation for all the studied factors except short-acting beta 2 (SABA) and day symptom improvement.
Conclusion We conclude that the decrease of airway acidity by NaHCO3 8.4% leads to significant decrease in inflammatory cells and frequency of exacerbation and improves pulmonary function in poorly controlled bronchial asthma.

Keywords: airway acidity, inhalation NaHCO3, pH change, uncontrolled bronchial asthma

How to cite this article:
Rezk NA, Alshamy A, Shehta M, Morsy NE, Alnahas M. Changing the airway pH: is it helping asthma control?. Egypt J Chest Dis Tuberc 2021;70:48-53
How to cite this URL:
Rezk NA, Alshamy A, Shehta M, Morsy NE, Alnahas M. Changing the airway pH: is it helping asthma control?. Egypt J Chest Dis Tuberc [serial online] 2021 [cited 2021 Dec 5];70:48-53. Available from: http://www.ejcdt.eg.net/text.asp?2021/70/1/48/312150   Introduction 

Asthma is a heterogeneous disease characterized usually by chronic airway inflammation. It is defined by a history of respiratory symptoms such as wheezes, shortness of breath, chest tightness, and cough that vary over time and intensity, together with variable airway obstruction [1].

The pathophysiology of asthma appears to be related to increased airway acidity, which may lead to bronchoconstriction, increased mucus viscosity, impaired ciliary motility, and epithelial damage [2],[3].

Airway pH has been assessed either using invasive maneuvers that are not accepted in routine practice, or by exhaled breath condensate (EBC), which carries a high risk of possible digestive contamination of the collected sample. In addition, a small amount of epithelial lining fluid is collected [4],[5]. Nevertheless, induced sputum provides a large amount of epithelial lining fluid that can help in assessment of the degree of airway inflammation. Besides, it is a feasible, simple, and noninvasive technique [6],[7].

It was previously reported that asthmatic individuals have lower pH compared with healthy individuals. Furthermore, the lowest induced sputum pH was detected in cases with poorly controlled asthma [8].

There is a great controversy regarding the relation between symptoms and airway inflammation, especially in complex asthma [9]. Symptom perception may be influenced by several factors, including obesity [10] and the coexistence of anxiety and depression [11]. Besides, the inaccurate perception of asthma symptoms is highly variable within persons [12].

Therefore, there is a need for objective evaluation of asthma symptoms and control, suggesting a possible role for biomarkers of airway inflammation. This may further facilitate management decisions, as the presence or absence of inflammation may be used to guide treatment plans [13],[14].

Even if significant differences in EBC pH between stable asthmatic and control groups are controversial, almost all authors agree that exacerbation and poor control of the disease leads to a decrease in pH values. Moderate, severe, or badly controlled asthma is connected with lower EBC pH values than cases that are mild or well controlled [15].

Nebulized NaHCO3 can increase airway pH without significant effects on exhaled CO2 levels in healthy participants. NaHCO3-induced increase in Qaw, together with elevated airway pH, could improve absorption of inhaled cationic bronchodilators [16].

We aimed in our study to evaluate the degree of asthma control by increasing pH in uncontrolled asthma cases by the use of inhaled NaHCO3 8.4% for 3 months.

  Patients and methods 

We studied 100 patients divided by simple randomization to 75 patients in the study group and 25 controls. The study was conducted in the outpatient clinics, Chest Department, Mansoura University Hospitals, Egypt, during the period between March 2014 and May 2018. IRB acceptance code was R.20.03.775.R1.

Cases diagnosed with uncontrolled or partially controlled BA, whose age was more than 18 years, were included in our study. Conversely, uncooperative cases, presence of reflux symptoms, and exacerbated asthma were causes of exclusion.

All study participants were subjected to the following:

Complete history taking and clinical examination.Routine investigations.Sputum total and differential cell count and pH measurements in sputum.Pulmonary function tests with postbronchodilator forced expiratory volume in 1 s (FEV1) measurements.High-resolution computed tomography to exclude other diseases that may be associated with BA.Sputum induction and NaHCO3 8.4% inhalation by jet nebulizer 3 ml every 8 h for 3 months to all studied patients.Evaluation of asthma exacerbation 6 months before and after intervention.

Sampling and processing of induced sputum

Induced sputum was performed according to the recommendations of the European Respiratory Society task force [17],[18]. Both FEV1 and forced vital capacity (FVC) were assessed at baseline and following salbutamol inhalation (200 μg by metered dose inhalers). Then, cases were asked to rinse their mouth. Participants inhaled sterile hypertonic saline (NaCl, 4.5%) nebulized with an ultrasonic device at 1 ml/min for three cycles of 5 min each. Cases were asked to cough on a sterile dish after each cycle or when needed. Cell count was carried out on at least two slides for an overall differential count of 800 nucleated nonsquamous cells. Samples were considered suitable if they contain less than 20% squamous cell contamination (to exclude salivary contamination), and more than 50% viable cells.

pH measurement

Without any additives, plugs were chosen from fresh induced-sputum samples, and careful aspiration was performed using a 1-ml insulin syringe. A 0.3–0.6 ml sample was considered sufficient for evaluation by the blood gas analyzer. To check for within-sample repeatability, three different samplings were performed in each sample, and they were analyzed separately immediately after sputum production. Then, the mean pH of each patient’s sputum was measured.

  Results 

The mean age of the included cases was 48.07 and 48.2 years in the study and control groups, respectively. There was no significant difference between study and control groups regarding demographic data, all basic investigations, pulmonary function, or sputum total and differential cells. These data are shown in [Table 1] and [Table 2].

As illustrated in [Table 3], sputum pH increased significantly in the study group. Four symptoms assessment improve significantly in both groups, whereas frequency of exacerbations was statistically decreased in the study group (SABA use, day time symptoms, night symptoms and limitation of activity). Moreover, erythrocyte sedimentation rate decreased significantly after first hour in both groups after treatment.

Table 3 Sputum pH, parameters of control assessment, exacerbation, erythrocyte sedimentation rate, sputum total and differential cells count, and spirometry in study group before and after treatment and control group before and after treatment

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Both FEV1 and FVC improved significantly in both groups after treatment. Sputum total cell count, neutrophils, eosinophils, along with lymphocytes decreased significantly in the study group after treatments, but sputum lymphocytes only decreased significantly in control group after treatment.

As shown in [Table 4], when we compared both groups after treatment, we found a significant increase of sputum pH after treatment in the study group. Furthermore, significant improvement of FEV1, FVC, four parameters of control assessment, and exacerbation also improved in study group after treatment. There was a significant decrease of total cells and eosinophils in sputum in the study group.

In [Table 5], the linear regression model showed a significant negative correlation for all the studied factors except short-acting beta 2 and day symptom improvement.

Table 5 Correlation between pH difference and difference in other follow-up parameters

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  Discussion 

The first problem faced by us in our research was how we can assess the pH in sputum without measurement of breath condensate. Therefore, we based on Kodric et al. [8], who measured the sputum pH by pH meter and repeated it after 48 h in 57 outpatients, and concluded that induced sputum is a feasible, repeatable, and noninvasive method to measure airway pH.

We studied 100 patients with uncontrolled asthma; 75 patients received NaHCO3 8.4% 3 ml every 8 h by nebulizer plus step up, and 25 patients in control group was step up only.

The theory postulates that the severity of asthma control correlates with the increase in the airway acidity, so we tried to change the airway pH, and then we assessed our cases for the symptoms of control assessment in addition to different related inflammatory markers.

Before our intervention, both groups were comparable in all measured parameters. We found that sputum pH increased significantly in the study group, and this was caused by inhalation of NaHCO3, and that proved to be successful in changing airway pH. The four symptoms of assessment control improved significantly in both groups, whereas the frequency of exacerbations was statistically decreased in the study group.

Moreover, erythrocyte sedimentation rate decreased significantly after first hour in both groups after treatment. Both FEV1 and FVC improved significantly in both groups after treatment. Sputum total cell count and neutrophils, eosinophils, as well as lymphocytes decreased significantly in the study group after treatment, but only sputum lymphocytes decreased significantly in the control group after treatment.

When we compared both groups after treatment, we found a significant improvement of parameters of control in the study group compared with the control group. Moreover, the spirometer parameters and frequency of exacerbation improved significantly in the study group. Besides, total sputum cell count and eosinophils decreased significantly in the study group after treatment.

Kodric et al. [8] concluded that patients with asthma showed lower pH than healthy participants. Patients with poorly controlled asthma seem to have the lowest induced-sputum pH, independent of the Global Initiative for Asthma severity level.

Airway pH changes may form an integral part of the innate host immune response. However, it is incriminated in the pathogenesis of obstructive airway diseases like asthma. Acid-induced asthma appears in association with gastroesophageal reflux after accidental inhalation of acid (fog, pollution, and workplace exposure) and in the presence of altered airway pH homeostasis. Endogenous and exogenous exposures to acids evoke cough, bronchoconstriction, airway hyperreactivity, microvascular leakage, and heightened production of mucous, fluid, and nitric oxide. Abnormal acidity of the airways is reflected in exhaled breath assays [2].

The intimate mechanisms of acid-induced airway obstruction are dependent on activation of capsaicin-sensitive sensory nerves. Protons activate these nerves with the subsequent release of tachykinins. These mediators, in conjunction with nitric oxide, oxygen radicals, and proteases, modulate diverse aspects of airway dysfunction and inflammation. The recognition that acid stress might initiate or exacerbate airway obstructive symptomatology has prompted the consideration of new therapies targeting pH homeostasis [2].

In another study, exhaled NO(FeNO) and EBC pH after argon deaeration were measured in 274 consecutive patients. Asthma control was evaluated by two asthma specialists blinded to FeNO and pH measurements. Authors found that FeNO was higher and EBC pH was lower in patients with not well-controlled compared with controlled asthma, and they concluded that FeNO and EBC pH levels may identify patients with not well-controlled asthma [19].Even if significant differences in EBC pH between stable asthmatic and control groups are controversial, almost all authors agree that exacerbation and poor control of the disease leads to a decrease in pH values. Moderate, severe, or badly controlled asthma is connected with lower EBC pH values than cases that are mild or well controlled [15].

Liu et al. [20] found that low EBC pH was associated with high BMI, high BAL neutrophil counts, low prebronchodilator FEV1 ratio, high allergy symptoms, race other than white, and gastroesophageal reflux symptoms.

  Conclusion 

We conclude that the decrease of airway acidity by NaHCO3 8.4% leads to significant decrease in inflammatory cells and frequency of exacerbation and improves pulmonary function in poorly controlled bronchial asthma.

Recommendations

We recommend repeating the study in a large number of patients, with the provision of NaHCO3 in metered dose inhaler to facilitate use of it in future studies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]