Tuberculosis and chronic nonspecific lung diseases

In their daily clinical work, phthisiologists and pulmonologists often encounter the problem of the relationship between chronic non-specific lung diseases (CNLD) and tuberculosis. The frequency of CNLD in patients with pulmonary tuberculosis ranges from 12-15 to 90% with a tendency to increase in frequency in destructive and chronic forms. This chapter examines two diseases: bronchial asthma and chronic obstructive pulmonary disease - in combination with tuberculosis of the respiratory organs.

Tuberculosis often joins with chronic tuberculosis (paratuberculous process), two diseases can occur in one patient simultaneously (metatuberculosis process). Chronic tuberculosis sometimes develops as a result of tuberculosis against the background of residual changes (post-tuberculous process). Chronic tuberculosis contributes to the development of obstructive disorders or increases them, aggravates disturbances of mucociliary clearance and makes them diffuse. The use of systemic glucocorticoids can lead to the development or exacerbation of tuberculosis.

Chronic obstructive pulmonary disease is a preventable, treatable condition characterized by airway obstruction that is not fully reversible. The airway obstruction, usually progressive, is due to an abnormal inflammatory response of the lungs to exposure to noxious particles or gases, primarily tobacco smoke. Although COPD affects the lungs, the disease also causes significant systemic dysfunction.

The course of tuberculosis in patients with COPD is less favorable. It is necessary first of all to examine sputum for the presence of non-tuberculous microflora and its resistance to antibiotics, and also to determine the function of external respiration (spirogram and flow-volume curve) with an assessment of the reversibility of broncho-obstructive syndrome (test-inhalation of a bronchodilator in the presence of obstruction). In most cases, patients with COPD are smokers. It is known that tobacco smoke affects not only humans, but also mycobacteria, increasing, on the one hand, cases of their mutations with the formation of antibiotic-resistant forms, and on the other hand, activating their metabolism and tendency to reproduce, i.e. increasing the effectiveness of treatment with respect to sensitive strains. With age, the number of patients with pulmonary tuberculosis in combination with COPD increases.

According to the severity, COPD is divided into four stages based on clinical manifestations and spirogram parameters.

Treatment of chronic non-specific lung diseases in tuberculosis

Basic therapy for stable moderate to severe COPD are short-acting (ipratropium bromide) and long-acting (tiotropium bromide) anticholinergics; a fixed combination with β ₂ -adrenergic agonists (ipratropium bromide with fenoterol, ipratropium bromide with salbutamol) can be used. The delivery form (metered-dose inhaler, dry powder inhaler or nebulizer) is selected by the physician based on the availability of the drug, the patient's skills and capabilities, and individual tolerance. The effectiveness of these drugs has been proven in patients with tuberculosis of the respiratory organs with broncho-obstructive syndrome. Inhaled glucocorticoids (IGCS) should be used only with a positive test (IGCS test therapy under spirometry control before and after treatment). With an increase in FEV1 _by 12-15% (and not less than 200 ml), it is advisable to use ICS or fixed combinations of ICS and long-acting β2 _- adrenergic agonists (budesonide with formoterol, fluticasone with salmeterol). Slow-release theophyllines are the drugs of choice, but due to the high probability of side effects, preference is given to inhaled drugs. Theophylline metabolism is impaired by rifamycins. Systemic glucocorticoids, recommended for COPD as a two-week test therapy, are used with caution in tuberculosis and only against the background of full-fledged complex etiotropic therapy. Mucolytics and mucoregulators (ambroxol, acetylcysteine) are prescribed only in the presence of difficult-to-separate sputum.

In case of exacerbation of COPD, short-acting β ₂ -adrenergic agonists or combination drugs (a metered-dose aerosol inhaler with a spacer or via a nebulizer) are used. A short course of systemic steroids (for example, prednisolone with 30 mg per day orally for 14 days) is administered only to compliant patients receiving full complex treatment and having no contraindications to corticosteroid therapy. In severe cases, non-invasive mechanical ventilation, transfer of the patient to the intensive care unit, and the use of low-flow oxygen therapy are recommended.

Antibacterial therapy is prescribed to patients with COPD in the presence of signs of bacterial infection (increased amount of sputum, change in sputum color - yellow or green, appearance or increase in fever). The drugs of choice are aminopenicillins with β-lactamase inhibitors, new macrolides (azithromycin, clarithromycin), "respiratory" fluoroquinolones (levofloxacin, moxifloxacin, gemifloxacin). It should be noted that many fluoroquinolones are effective against Mycobacterium tuberculosis and can be included in treatment regimens for resistant forms of tuberculosis.

Bronchial asthma is a chronic inflammatory disease of the airways involving many cells and cellular elements. Chronic inflammation is associated with bronchial hyperreactivity, which leads to recurrent episodes of wheezing, shortness of breath, chest tightness and cough, especially at night or in the early morning. It is usually associated with diffuse but variable airflow obstruction, which is often reversible, either spontaneously or with treatment. Patients with asthma are more likely to develop allergic reactions to medications.

According to federal protocols, bronchial asthma has four degrees of severity.

Step 1 - drugs "on demand".

Patients with short-term daytime symptoms occurring from time to time (≤2 per week during the day). No nighttime symptoms.

• Fast-acting inhaled β2 _- adrenergic agonist for symptom relief (<2/week during the day).
• If symptoms become more frequent and/or their severity periodically increases, regular continuous therapy (step 2 or higher) is indicated.

Step 2. One of the drugs of continuous therapy + therapy

• Low dose ICS as initial chronic therapy at any age.
• Alternative continuous therapy with leukotriene antagonists when patients are unable/unwilling to use ICS.

Step 3. One or two drugs for continuous therapy + drugs “on demand”.

• For adults - a combination of low doses of ICS with a long-acting inhaled β ₂ -adrenergic agonist in one inhaler (fluticasone + salmeterol or budesonide + formoterol) or in separate inhalers
• A long-acting inhaled beta ₂ -adrenergic agonist (salmeterol or formoterol) should not be used as monotherapy.
• For children - increase the dose of ICS to average.

Additional level 3 - options for adults.

• Increase the dose of ICS to medium.
• Low doses of ICS in combination with leukotriene antagonists.
• Low dose sustained release theophylline.

Step 4. Two (always) or more drugs for continuous therapy + an “on-demand” drug.

• Medium or high doses of ICS in combination with a long-acting inhaled β2 _- adrenergic agonist.
• Medium or high doses of ICS in combination with a leukotriene antagonist.
• Low dose sustained release theophylline in addition to medium or high doses of ICS in combination with a long-acting inhaled β ₂ -adrenergic agonist.

Step 5. Additional drugs for continuous therapy + on-demand therapy.

• The addition of oral glucocorticoids to other drugs in chronic therapy may be effective, but significant side effects are possible.
• The addition of anti-IgE therapy to other drugs of continuous therapy improves control of atopic bronchial asthma in cases where control has not been achieved.

Treatment of bronchial asthma in patients with tuberculosis is carried out according to the same principles, but taking into account a number of features. The administration of systemic glucocorticoids and ICS should necessarily be accompanied by controlled intake of anti-tuberculosis drugs. The clearance of theophylline preparations when taking anti-tuberculosis drugs (especially rifampicins) is lower, the half-life is longer, which requires a reduction in the dose of theophylline group drugs, especially in older patients.