Tuberculosis & Cystic Fibrosis: Epidemiology, Diagnosis & Treatment

Posted on Oct 17, 2024 in Medicine & Health

Tuberculosis (TB)

Epidemiology

• 1/3 of the world population is infected
• 8.8 million new cases annually
• Mostly in developing countries
• MDR-TB and XDR-TB are increasing due to poor treatment (not following protocols)

Etiology

Causative Agents:

1. Mycobacterium Tuberculosis
2. Other: M. Bovis, M. Africanum, M. Microti

Transmission:

• Airborne particles spread from people with active TB
• Risk factors: Overcrowded areas

Clinical Presentation

Active Disease

• 10% of immunocompetent individuals with latent TB become active
• 90% of immunocompetent individuals remain healthy
• TB reactive in 1-2 years/decades later
• Seeded organ can become a site of reactivation
• Reactivation usually occurs due to immunosuppression

Lung TB: Diagnosis

• Mostly by X-ray and respiratory symptoms (cough > 3 weeks, hemoptysis, chest pain, dyspnea)
• Fever of unknown origin + positive tuberculin test

I. Chest X-ray:

• Nodular infiltrate above/behind clavicle suggests TB reactivation
• Middle and lower lung infiltrates are non-specific but suspicious

II. Sputum Exam:

• Confirmatory test
• Acid-fast bacilli, Ziehl-Neelsen stain
• Nucleic acid amplification test for TB

III. Drug Susceptibility Test:

• Should be done on initial isolates to identify an effective anti-TB regimen
• Can take up to 8 weeks

IV. Tuberculin Skin Test:

Result is based on the appearance of a wheal:

• 1-5 mm: Patients at high risk of developing active TB if infected, chest X-ray evidence of past TB, high risk like immunocompromised/HIV patients
• 5-10 mm: Patients with some risk factors, such as injection drug users, recent immigrants from high-prevalence areas, residents of high-prevalence areas
• >15 mm: Patients with no risk factors

Lung TB: Differential Diagnosis

Lung TB: Principles of Treatment

Hospital Indication:

• Serious concomitant illness
• To perform diagnostic procedures
• Social issues
• Respiratory isolation

Treatment Regimens:

I. 2 Months of Intensive Phase Therapy:

• Use 4 drugs (isoniazid [INH], rifampin [RIF], pyrazinamide [PZA], ethambutol [EMB]) given daily throughout this phase for 2 weeks
• Followed by doses 2-3 times/week for 6 weeks
• Daily therapy for MDR-TB and HIV patients

II. After 2 Months of Intensive 4-Drug Treatment:

• PZA and EMB are stopped depending on susceptibility

III. 4-7 Months, Continuation Phase Treatment:

• Depends on the result of susceptibility testing and the presence or absence of cavitary lesions
• If culture and smear are negative, culture is positive but nothing on X-ray: INH and RIF are continued for 4 weeks
• If X-ray shows cavitation and culture or smear is positive: INH and RIF are continued for 7 months at a higher dose
• In either regimen, EMB is stopped if the initial culture shows no resistance to it

IV. MDR-TB:

• Prolonged treatment, 18-24 months
• PZA with fluoroquinolone and other drugs are needed, 4-5 drugs are needed to hit the likely infective strain
• Surgical resection in persistent culture-positive MDR-TB or XDR-TB

V. Treatment of Latent TB:

• INH unless there is drug resistance, dose is 300 mg/day for 6-9 months
• RIF (alternative) 600 mg once daily for 4 months

VI. Prevention:

• Covering cough
• Respiratory isolation
• BCG vaccine (reduces extra thoracic TB in children)

Cystic Fibrosis (CF)

Epidemiology and Etiology

• CF is the most lethal genetic disease affecting the White population
• Autosomal recessive mutation in the CFTR gene on the short arm of the 7th chromosome

Genetic and Clinical Presentation

The CFTR gene encodes for proteins that serve as chloride channels.

1. Secretion and reabsorption of Cl- (depends on tissue): For example, in the sweat glands, CFTR leads to reabsorption of chloride, while in the bronchial and intestinal epithelium, it leads to its secretion.
2. Regulation of additional ion channels and cellular processes: (such as some K+ channels, Na+ channels)
3. Regulation of bicarbonate secretion

CF Manifestations

Diagnosis

Treatment

Goals:

• Prevent pulmonary infections
• Optimize nutrition
• Encourage physical activity
• Address psychological well-being

Treatment and Prevention of Pulmonary Problems:

• Prophylactic vaccines (influenza, pneumococcal)
• Bronchodilators
• Chest physiotherapy
• NSAIDs
• Lung transplant

Gastrointestinal Treatment:

• Stool softeners
• Dietary modifications
• Pancreatic enzyme replacement therapy

Alpha-1 Antitrypsin Deficiency

What is it?

• Congenital lack of primary lung antiprotease
• Results in protease-mediated tissue destruction and emphysema in adults
• Hepatic accumulation of abnormal alpha-1 antitrypsin can cause liver disease

Diagnosis

1. Suspected in: Smokers > 45 years old, non-smokers with occupations prone to emphysema, patients with panniculitis, neonates with jaundice or liver enzyme elevation
2. Serum alpha-1 antitrypsin level < 80 mg/dL
3. Patients with low serum alpha-1 antitrypsin levels should undergo genotyping

Treatment

1. Purified human alpha-1 antitrypsin to maintain alpha-1 antitrypsin levels > 80 mg/dL
2. Smoking cessation
3. Bronchodilators
4. Treatment of respiratory infections
5. Liver treatment is supportive, and transplantation of the liver in case of liver failure

Congenital Lung Diseases and Their Diagnosis

Important causes of morbidity in infants, children, and adults.

Evaluation requires imaging and surgical correction of the anomaly.

Anomalies Include:

• Pulmonary underdevelopment
• Scimitar syndrome
• Congenital cystic adenomatoid malformation (CCAM)
• Congenital lobar emphysema (CLE)
• Pulmonary sequestration

Pulmonary Underdevelopment

Groups:

1. Agenesis
2. Aplasia
3. Hypoplasia

I. Pulmonary Agenesis

General:

• Occurs in the embryogenic period (week 4)
• Abnormality is unilateral
• No gender preference
• May involve other systems as well: gastrointestinal, genitourinary, skeletal
• Contralateral lung has compensatory hypertrophy

Diagnosis:

• Chest radiograph: Completely opaque hemithorax with displacement of the mediastinum and diaphragm
• Usually involves the left upper lobe
• Normal contralateral lung with hyperinflation

II. Pulmonary Hypoplasia

• Deficient or incomplete development of the lung
• Bronchi and alveoli in the underdeveloped lobe
• Most common cause is congenital diaphragmatic hernia
• Another cause is extralobar sequestration

Diagnosis:

X-ray:

• Decreased aeration of the affected hemithorax and small thoracic cage
• Mediastinal displacement to the side of hypoplasia
• Accentuation during inspiration due to increased compensatory ventilation of the other lung

III. Congenital Cystic Adenomatoid Malformation (CCAM)

• Uncommon cause of respiratory distress characterized by a multicystic mass of pulmonary tissue with abnormal proliferation of bronchial structures
• Pathophysiology: Overgrowth of bronchioles with almost complete suppression of alveolar development between the 7th and 10th weeks of embryonic life
• Malformation Types:
• Type 1: Variable sized cysts, at least one dominant cyst
• Type 2: Smaller, more uniform cysts
• Type 3: Bronchoalveolar microcysts
• CCAM usually involves a single lobe

Diagnosis:

• Prenatal ultrasound to detect abnormalities
• Postnatal chest X-ray: Multiple air-filled, thin-walled cysts varying in size
• CT is useful to characterize CCAM

Congenital Lobar Emphysema (CLE)

Definition:

• Progressive overdistention of a lobe, sometimes of 2 lobes
• Pathophysiology: Check-valve mechanism at the bronchial level causing progressive hyperinflation
• Most commonly affects the left upper lobe
• No destruction of alveolar walls

Types:

1. Type 1: CLE with symptoms in infancy
2. Type 2: CLE with symptoms in older children
3. Type 3: CLE remains asymptomatic

Diagnosis:

• X-ray, CT: Hyperinflation of a segment or lobe

Pulmonary Sequestration

• Abnormal lung tissue mass that has no normal connection with the bronchial tree or pulmonary arteries

Types:

I. Intralobar Sequestration:

• Within the lung and has visceral pleura covering it
• Acquired abnormality of the lung

II. Extralobar Sequestration:

• Abnormal lung tissue that is surrounded by its own separate pleura
• Located in the posterior lower chest
• 90% of extralobar sequestrations are on the left side

Diagnosis:

• Best to diagnose in the prenatal and neonatal period
• Prenatal ultrasound: Hyperechoic mass in the posterior basal hemithorax
• Prenatal MRI: Sharp margins and high signal intensity
• CT scan: Soft tissue cystic mass containing air or fluid, focal emphysema