Tuberculosis & Cystic Fibrosis: Epidemiology, Diagnosis & Treatment
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:
- Mycobacterium Tuberculosis
- 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
TB | Pneumonia | Lung Abscess | Sarcoidosis |
---|---|---|---|
History of exposure (e.g., family member with active TB), cough > 3 weeks, hemoptysis, chest pain, dyspnea, unexplained illness, fever of unknown origin. Chest X-ray: nodular infiltrate above or behind the clavicle. Acid-fast bacilli (AFB) in sputum smear prepared with Ziehl-Neelsen stain. Biopsy specimen histology reveals caseous granulomas. Positive tuberculin skin test (TST) or interferon-gamma (IFN-γ) release by lymphocytes. | Presence of paraneoplastic syndromes. CT may confirm the diagnosis. PET-CT can help differentiate inflammatory and malignant processes. Cytopathology examination of pleural fluid or sputum may contain increased concentration of malignant cells. Bronchoscopy. | Aspiration-prone history. Culture of sputum or bronchoscopic aspirates. Anaerobic infection due to aspiration. Chest X-ray classically shows consolidation with a single cavity containing an air-fluid level. | X-ray: Hilar adenopathy. CT: Detects hilar and mediastinal lymphadenopathy. CT in later stages: Thickening of bronchovascular bundles and walls, blurring of interlobular septa. Biopsy tissue for mycobacteria. |
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
INH | RIF | PZA | EMB |
---|---|---|---|
5 mg/kg/day (max 300 mg) | 10 mg/kg/day (max 600 mg) | 40-55 kg: 1 g/day | 15-25 mg/kg/day |
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.
- 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.
- Regulation of additional ion channels and cellular processes: (such as some K+ channels, Na+ channels)
- Regulation of bicarbonate secretion
CF Manifestations
Organ System | Manifestations |
---|---|
Pulmonary | Recurrent chronic infections, cough with sputum production, hemoptysis, sleep disturbances |
Gastrointestinal | Pancreatic insufficiency, poor growth in children due to protein malabsorption, diabetes mellitus |
Integumentary | Excessive sweating, salt crystal formation on skin |
General | Growth retardation, osteoporosis |
Diagnosis
Test | Description |
---|---|
Clinical Presentation and History | Symptoms and family history suggestive of CF |
Sweat Test | Stimulation of localized sweating by pilocarpine. Chloride > 60 mEq/L confirms the diagnosis. |
Mutation Analysis | In patients with CF but normal sweat test. Diagnosis identifies 2 CF mutations. |
Other | Serum trypsin (elevated), 72-hour fecal fat (pancreatic function), secretin stimulation test, imaging (lung hyperinflation and bronchial wall thickening) |
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
- Suspected in: Smokers > 45 years old, non-smokers with occupations prone to emphysema, patients with panniculitis, neonates with jaundice or liver enzyme elevation
- Serum alpha-1 antitrypsin level < 80 mg/dL
- Patients with low serum alpha-1 antitrypsin levels should undergo genotyping
Treatment
- Purified human alpha-1 antitrypsin to maintain alpha-1 antitrypsin levels > 80 mg/dL
- Smoking cessation
- Bronchodilators
- Treatment of respiratory infections
- 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:
- Agenesis
- Aplasia
- 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:
- Type 1: CLE with symptoms in infancy
- Type 2: CLE with symptoms in older children
- 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