IHT in Combined Care for Childhood Asthma

Introduction

Bronchial asthma is a chronic airway disease and a serious healthcare problem in almost every country. It affects all ages and often has a severe, sometimes fatal course. More than 100 million people worldwide have asthma; childhood prevalence varies between populations from 0 to 30% [1].

Among obstructive lung diseases, asthma unquestionably leads in prevalence, severity and danger to children’s lives [2,3].

A clear connection between childhood and adult asthma has been established [4,5]. Childhood-onset asthma persists into adulthood in 60–80% of cases. Age-related symptom disappearance mainly occurs in mild disease [6]. Most researchers consider recovery merely a prolonged clinical remission that may be disrupted by various factors. Finding prevention and treatment methods during childhood and adolescence is therefore highly relevant.

Adaptation to reduced inspired oxygen partial pressure has long been known. Recent research showed that artificially reduced oxygen content and partial pressure at normal atmospheric pressure benefits asthma patients. Normobaric interval hypoxic training (IHT) entered medical practice in 1985. It does not cause complications or adverse effects [7,8]. However, dedicated studies are needed to establish evidence-based regimens, optimal inspired oxygen for different asthma severities, exposure duration and normoxic intervals. Conflicting findings on humoral and cellular immunity after hypoxic therapy prompted detailed investigation.

The aim was to evaluate normobaric IHT in combined treatment of children and adolescents with asthma.

Materials and methods

We examined 180 asthma patients in four groups: mild disease at 8–11 years, moderate disease at 8–11, mild disease at 12–18, and moderate disease at 12–18. Atopic asthma affected 114 patients, 63.4%; infectious-allergic asthma 66, 36.6%. An adverse premorbid background and familial allergic burden occurred in 68%. Exudative-catarrhal diathesis was found in 64%; allergies of various origins in 93%. ENT pathology—chronic tonsillitis, pharyngitis or rhinitis—affected 67.2%. In mild asthma, maintenance anti-inflammatory therapy was Intal in 21% and ketotifen in 45%. Moderate patients received Intal in 16%, Tilade in 41%, Flixotide in 20%, Ingacort in 10% and ketotifen in 14%.

All received bronchodilators during exacerbations.

Combined sanatorium treatment at the Raduga Republican Children’s Rehabilitation Centre in Nalchik comprised therapeutic massage, alkaline and oil inhalations, exercise therapy, physiotherapy and pool swimming. Medication continued as indicated.

All 180 completed normobaric IHT. A control group of 50—28 with mild and 22 with moderate asthma—received general sanatorium treatment alone.

All underwent FVC, first-second forced expiratory volume FEV1, FEV1/FVC Tiffeneau index, peak expiratory flow PEF and maximal expiratory flow at 50% FVC, MEF50%, on the SPIROSIFT SP-5000 computerised spirograph.

Obstruction and respiratory impairment were graded using the 1995 European Respiratory Society recommendations: persistent FEV1 below 50% predicted indicated severe impairment, 50–69% moderate and above 70% mild.

FEV1 increase was calculated relative to predicted FEV1. A positive bronchodilator response required ΔFEV1 of at least 15% of predicted.

Particular attention was paid to respiratory-system function during reduced inspired oxygen and throughout IHT. Respiratory and body oxygen-regime measures followed A.Z. Kolchinskaya. Minute ventilation, tidal volume and respiratory rate used a VEB MEDIZINTECHNIK volumeter, Germany. Inspired, expired and alveolar oxygen used an INSOVT analyser, St Petersburg. Oxygen consumption followed Douglas–Haldane; blood pressure Korotkoff. SaO2 and heart rate were recorded with an Oxyshuttle pulse oximeter, Sensor-Medicus, USA. Cardiac output in children/adolescents followed L.M. Pugina, and haemoglobin was measured on FEK-M.

Noninvasive assessment of the lung surfactant system in exhaled air has become widespread. Exhaled breath condensate, EBC, was collected by a modified G.I. Sidorenko method. Respiratory moisture loss was characterised by measuring/calculating exhalate volume over ten minutes. EBC lactate dehydrogenase, LDH, total lipids and proteins were measured photoelectrocolorimetrically; pH used OP-270, Radelkis, Hungary.

EBC surface tension used Kh.B. Khakonov’s large-drop method. Total EBC protein was quantified in short-wave ultraviolet by measuring protein absorption and deriving its concentration.

Cortical biopotentials were recorded on a 19-channel EEG with histogram and brain-mapping display in bilateral occipital O1/O2, parietal P3/P4, central Cz, temporal T3/T4 and frontal F3/F4 areas. Recording lasted 15–20 minutes and included resting/background EEG and functional challenges: eye opening/closure, rhythmic photic stimulation and hyperventilation. A 19-channel software-controlled biopotential amplifier recorded EEG.

Immune assessment measured serum IgA, IgM and IgG by Mancini, 1965; total IgE by enzyme immunoassay; and circulating immune complexes by precipitation in 3.75% polyethylene glycol.

Evidence-based statistical processing used descriptive statistics, discriminant, factor and cluster analyses [9,10].

Results and discussion

IHT was highly effective: after treatment 65.8% of children and 58.4% of 12–18-year-olds showed a lower acetylcholine sensitivity threshold, interpreted as reduced bronchial hyperreactivity. Bronchodilator use could be reduced by 25.3% in mild and 14.8% in moderate asthma; antihistamines by 34.1% and 15.3%, respectively. Treatment-effect analysis by disease form indicated greater efficacy in atopic asthma.

Bronchial patency improved significantly in all patients after IHT. In mild asthma, FVC increased by 1.5±0.01%, FEV1 by 4.1±0.1%, PEF by 7.3±0.2%, and airflow through large, medium and small bronchi by an average of 6.3±0.1%. During remission, bronchial patency in these patients was not substantially abnormal and practically matched age-related norms. IHT therefore changed bronchial patency only slightly in this category.

Moderate asthma showed significant respiratory improvement, p<0.05: FVC +16.0±0.7%, FEV1 +16.2±1.4%, PEF +25.7±1.7%, and large-, medium- and small-bronchial flow +16.4±1.1%, +18.1±0.8% and +25.6±1.4%. Thus IHT substantially improved patency in moderate disease.

Peak-flow monitoring showed that successful IHT increased PEF from 50.0±2.5% predicted at the first session to 85.4±3.4% at the last, while daily PEF variation fell from 1.00±0.02 to 0.10±0.04 L/s. This indicated reduced tracheobronchial hyperreactivity and obstruction.

All respiratory-system components improved. In moderate asthma, tidal volume increased significantly by 10.62±1.1% at 8–11 years and 14.6±1.2% at 12–18. The alveolar/minute ventilation ratio rose to an average 75.6±2.4% (Table 1), indicating improved ventilation and less functional dead space and favourable conditions for gas exchange between alveolar air and venous blood.

EBC volume increased after IHT. Mild asthma reached the age-normal range of 2.2 mL per ten minutes; moderate asthma increased to 1.67±0.03 mL per ten minutes on average.

EBC surface tension did not change significantly in mild asthma. In moderate asthma it fell significantly to 59.3±2.0 dyn/cm at 8–11 years and 60.4±1.5 dyn/cm at 12–18 (Table 2).

Mild-asthma EBC LDH content/activity was little altered before IHT and showed no significant treatment change. In moderate asthma, LDH activity declined significantly, increasing condensate pH.

Condensate pH was normal in mild asthma at both ages. In moderate asthma pH rose significantly. Total EBC protein and lipid concentrations decreased after IHT (Table 3).

These changes indicated increased pulmonary moisture formation/excretion, better surfactant properties, reduced alveolar-capillary membrane permeability and greater tissue oxygen consumption. Positive pulmonary metabolic effects of hypoxic adaptation led to clinical improvement and a more favourable asthma course.

IHT benefited circulation and blood oxygen transport. Cardiac work became more economical. Stroke volume increased while cardiac output remained relatively unchanged. Better ventilation–perfusion relationships raised arterial oxygen saturation.

Haemoglobin increased an average 6.1±0.2% in all patients during adaptation. Some gained up to 15 g/L after 15 sessions. Higher haemoglobin, blood oxygen capacity and arterial saturation increased arterial oxygen content by an average 7.86±0.2% (Table 4).

Oxygen utilisation improved, the arteriovenous oxygen difference increased and tissue oxygen consumption rose significantly in all asthma patients.

These respiratory, circulatory and blood respiratory-function changes altered body oxygen regimes after IHT. An important result was less arterial hypoxaemia. Respiratory and circulatory economy improved significantly, p<0.05, through lower ventilatory and haemodynamic equivalents and substantial increases in oxygen pulse and the oxygen effect of each respiratory cycle.

Repeat hypoxic testing after IHT demonstrated increased hypoxia resistance and adaptation to hypoxic hypoxia.

IgA increased after IHT, a favourable component of combined asthma treatment aimed at greater resistance to infection and exacerbation triggers (Table 5).

IgG increased and IgE decreased. The IgE/IgG ratio is an important treatment-effectiveness indicator. Increased serum IgG presumably shifted T-helper differentiation from Th2 to Th1, inhibiting B-cell IgE synthesis, reducing allergy-mediator release and inflammatory intensity.

Immune changes at 12–18 years were less marked than at 8–11, explainable by pubertal/prepubertal immune characteristics. Clinical manifestations were consequently more persistent in the older group (Table 6).

IHT thus achieved an optimal redistribution of immune parameters, improving clinical asthma in both atopic and infectious-allergic forms.

Cortical bioelectrical activity normalised after IHT. Regional amplitude differences approached normal, indicating positive electrical changes. EEG normalisation and synchronisation resulted from improved oxygen delivery at every transfer stage, greater cerebral consumption and training of respiratory enzymes. Alpha rhythm became more regular; its index and amplitude increased substantially in almost all lobes. Beta index also rose in many leads toward healthy age-matched values. Theta and delta indices decreased significantly in moderate asthma, indicating less cerebral hypoxia. Biopotentials synchronised across almost all lobes and rhythm-distribution asymmetry diminished.

Conclusion

The findings clearly showed substantial benefit of hypoxic adaptation during IHT for children and adolescents with asthma. Clinical improvement was explained by normalised respiratory-system function, pulmonary surfactant, body oxygen regimes and immune reactivity. Better oxygen supply throughout transport and increased tissue consumption improved cortical bioelectrical activity. Thus, high effectiveness of IHT within combined childhood/adolescent asthma treatment was demonstrated.

Immune parameters — 8–11

Statistical symbols follow the original; * p<0.05 versus baseline.

Immune parameters — 12–18

Statistical symbols follow the original; * p<0.05 versus baseline.

Full table 1 — PDF, 4

Full table 2 — PDF, 4

Full table 3 — PDF, 5

Full table 4 — PDF, 5

References

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8. Ткачук Е.Н., Горбаченков А.А., Колчинская А.3. и др. Адаптация к интервальной гипоксии с целью профилактики и лечения // Адаптационная медицина, механизмы и защитные эффекты адаптации. – Hipoxia Medical Ltd. – М., 1993. – С. 303–331.

9. Айвазян С.А., Мхитарян В.С. Прикладная статистика и основы эконометрики. Учебник для вузов. – М., 1998. – 1022 с.

10. Леонов В.П., Ижевский П.В. Прикладная статистика в медицине. //Междунар. журнал мед. практики. – 1998. – № 4. – С. 7–15.

Full main-text translation of: Борукаева И.Х. Эффективность интервальной гипоксической тренировки при бронхиальной астме у детей и подростков. Педиатрия. 2007;86(4):29–35.

Борукаева И.Х. Эффективность интервальной гипоксической тренировки при бронхиальной астме у детей и подростков. Педиатрия. 2007;86(4):29–35. — PDF

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