39.3 Pulmonology and Critical Care: Acute Respiratory Failure and Oxygen Therapy, Bronchial Asthma, COPD, Community- and Hospital-Acquired Pneumonia, Pulmonary Tuberculosis and TB Infection, Pulmonary Embolism, Lung Cancer and ARDS

Why this area matters

The Philippines has one of the highest TB burdens in the world, and pneumonia is among the leading causes of death. COPD from smoking and biomass smoke, asthma and lung cancer (a leading cause of cancer death in Filipino men) are frequent. The PLE asks for oxygen targets, ventilation choices, antibiotic regimens by risk class, and TB program rules.

Acute respiratory failure

• Type 1 (hypoxemic): PaO2 below 60 mmHg with normal or low PaCO2, from V/Q mismatch (pneumonia, PE, asthma), shunt (ARDS, atelectasis, edema) or diffusion problems. The A-a gradient is raised.
• Type 2 (hypercapnic): PaCO2 above 45 to 50 mmHg from hypoventilation: COPD and asthma exhaustion, drug overdose (opioids, sedatives), neuromuscular disease (Guillain-Barré, myasthenia, snakebite neurotoxicity), chest wall disease and obesity hypoventilation. The A-a gradient is normal in pure hypoventilation.
• Oxygen targets:
  • SpO2 92% to 96% for most acutely ill adults (avoid hyperoxia);
  • 88% to 92% for those at risk of hypercapnia (COPD, obesity hypoventilation, neuromuscular disease), using controlled oxygen (Venturi mask).
• Support:
  • high-flow nasal cannula for hypoxemic failure;
  • non-invasive ventilation (BiPAP) for hypercapnic COPD exacerbations and cardiogenic pulmonary edema;
  • intubation for failure of non-invasive support, coma, inability to protect the airway, or shock.
• Massive hemoptysis: protect the airway, lie the patient bleeding side down, and arrange bronchial artery embolization. TB, bronchiectasis and lung cancer are the common causes.

Bronchial Asthma

Bronchial asthma is a heterogeneous chronic airway disease characterized by chronic airway inflammation, bronchial hyperresponsiveness, and variable, reversible expiratory airflow limitation.

Diagnostic Hallmarks & Spirometry

• Variable Airflow Limitation: Spirometry remains the diagnostic cornerstone. A positive bronchodilator reversibility test is defined as an increase in $\text{FEV}_1$ of $> 12\%$ and $> 200\text{ mL}$ compared to baseline, 10 to 15 minutes after inhaling $200-400\text{ }\mu\text{g}$ of salbutamol/albuterol.
• Peak Expiratory Flow (PEF) Variability: Excessive diurnal variation in PEF ($> 10\%$ in adults based on twice-daily readings over 1 to 2 weeks).
• Bronchial Provocation Testing: When baseline spirometry is normal, bronchoprovocation with inhaled methacholine or histamine demonstrating a $\text{PC}_{20}$ (provocative concentration causing a $20\%$ fall in $\text{FEV}_1$) $\le 8\text{ mg/mL}$ establishes hyperresponsiveness.

Global Initiative for Asthma (GINA) Management Framework

GINA fundamentally transformed asthma care by eliminating short-acting beta-2 agonist (SABA) monotherapy due to increased risks of fatal exacerbations:

• Track 1 (Preferred Strategy): Low-dose inhaled corticosteroid (ICS)-formoterol used as both daily maintenance (or PRN in mild disease) and the as-needed reliever across all steps (Steps 1 to 5). Formoterol provides rapid-onset bronchodilation comparable to salbutamol within 1 to 3 minutes while delivering a concomitant anti-inflammatory dose of ICS.
• Track 2 (Alternative Strategy): Maintenance ICS plus as-needed SABA reliever. Daily adherence to ICS is strictly required before prescribing SABA.
• Stepwise Titration:
  • Steps 1-2: As-needed low-dose ICS-formoterol alone.
  • Step 3: Low-dose maintenance ICS-formoterol + as-needed reliever.
  • Step 4: Medium-dose maintenance ICS-formoterol + as-needed reliever.
  • Step 5: High-dose maintenance ICS-formoterol, add-on long-acting muscarinic antagonist (LAMA, tiotropium), and targeted biologics (e.g., Omalizumab for anti-IgE; Mepolizumab, Benralizumab for eosinophilic asthma targeting IL-5; Dupilumab targeting IL-4/IL-13).

Acute Severe Asthma (Status Asthmaticus)

An acute exacerbation unresponsive to standard outpatient bronchodilators, presenting with tachypnea, pulsus paradoxus, intercostal retractions, and diaphoresis.

• Life-Threatening Signs: "Silent chest" (absence of wheezing due to severe airflow limitation), cyanosis, bradycardia, confusion, exhaustion, and pseudonormal or elevated $\text{PaCO}_2$ ($> 42\text{ mmHg}$). In a hyperventilating asthmatic, $\text{PaCO}_2$ should be low; a normal or rising $\text{PaCO}_2$ heralds impending respiratory arrest.
• Emergency Management:
  1. Supplemental oxygen to maintain $\text{SpO}_2$ 93% to 95%.
  2. Repetitive or continuous nebulized SABA (salbutamol $2.5-5.0\text{ mg}$) combined with inhaled ipratropium bromide ($0.5\text{ mg}$) every 20 minutes for the first hour.
  3. Early systemic corticosteroids: oral prednisone $40-50\text{ mg}$ or intravenous hydrocortisone $100-200\text{ mg}$ / methylprednisolone $60-80\text{ mg}$.
  4. Intravenous Magnesium Sulfate ($2\text{ g}$ over 20 minutes) for severe refractory exacerbations.
  5. Mechanical ventilation: Avoid hyperventilation; tolerate permissive hypercapnia; maintain low respiratory rates and prolonged expiratory times ($I:E$ ratio $1:3$ to $1:4$) to prevent dynamic hyperinflation (auto-PEEP) and tension pneumothorax.

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Chronic Obstructive Pulmonary Disease (COPD)

COPD is characterized by persistent, progressive airflow limitation resulting from chronic inflammatory responses in airways and lung parenchyma to noxious particles, primarily cigarette smoke and biomass fuel exposure.

Diagnostic Criteria & GOLD Classification

• Diagnostic Hallmark: A post-bronchodilator $\text{FEV}_1/\text{FVC} < 0.70$ establishes persistent, non-fully reversible airflow obstruction.
• GOLD Spirometric Grades (based on post-bronchodilator $\text{FEV}_1\%$ predicted):
  • GOLD 1 (Mild): $\text{FEV}_1 \ge 80\%$ predicted.
  • GOLD 2 (Moderate): $50\% \le \text{FEV}_1 < 80\%$ predicted.
  • GOLD 3 (Severe): $30\% \le \text{FEV}_1 < 50\%$ predicted.
  • GOLD 4 (Very Severe): $\text{FEV}_1 < 30\%$ predicted.

Pharmacologic Maintenance (GOLD ABE Schema)

• Initial Maintenance: Inhaled long-acting muscarinic antagonists (LAMA: tiotropium) and/or long-acting beta-2 agonists (LABA: indacaterol, formoterol). Group A starts with a single bronchodilator; LAMA + LABA combination is first-line for Group B (more symptoms) and Group E (exacerbations).
• Inhaled Corticosteroids (ICS): Reserved as add-on therapy (triple therapy: LAMA + LABA + ICS) in patients with frequent exacerbations ($\ge 2$ per year or $\ge 1$ leading to hospitalization) AND blood eosinophil counts $\ge 300\text{ cells/}\mu\text{L}$ (or $\ge 100\text{ cells/}\mu\text{L}$ with repeated exacerbations). ICS is avoided when repeated pneumonia episodes occur.
• Interventions Proven to Reduce Mortality in COPD:
  1. Smoking Cessation: The single most effective intervention to halt accelerated decline in $\text{FEV}_1$.
  2. Long-Term Oxygen Therapy (LTOT): Administered $\ge 15\text{ hours/day}$ for resting chronic hypoxemia ($\text{PaO}_2 \le 55\text{ mmHg}$ or $\text{SpO}_2 \le 88\%$, or $\text{PaO}_2 56-59\text{ mmHg}$ if cor pulmonale, right heart failure, or secondary polycythemia is present).
  3. Lung Volume Reduction Surgery (LVRS): In highly selected patients with severe upper-lobe emphysema and low exercise capacity.

Acute Exacerbations of COPD (AECOPD)

• Anthonisen Criteria for Antibiotic Use:
  1. Increasing dyspnea.
  2. Increasing sputum volume.
  3. Increasing sputum purulence. Recommendation: Antibiotics are indicated if all three cardinal symptoms are present (Type 1), or if increased purulence is present plus one other symptom (Type 2). Common regimens: Amoxicillin-clavulanate, azithromycin, or respiratory fluoroquinolones for 5 to 7 days.
• Systemic Corticosteroids: Oral prednisone $40\text{ mg}$ once daily for 5 days accelerates recovery and prevents relapse.
• Non-Invasive Positive Pressure Ventilation (NIPV / BiPAP): The primary ventilatory modality of choice for acute hypercapnic respiratory acidosis ($\text{pH} < 7.35$ and $\text{PaCO}_2 > 45\text{ mmHg}$). NIPV reduces intubation rates, hospital stay, and in-hospital mortality.

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Community-Acquired Pneumonia (CAP)

Community-acquired pneumonia is an acute infectious inflammation of the lower respiratory tract in non-hospitalized individuals.

Clinical Risk Stratification: CURB-65 & Philippine CPG Guidelines

Empiric Antimicrobial Regimens

• Outpatient Low-Risk CAP (Healthy, No Comorbidities): High-dose oral Amoxicillin ($1\text{ g}$ TID) or Azithromycin ($500\text{ mg}$ Day 1, then $250\text{ mg}$ Days 2-5) or Doxycycline ($100\text{ mg}$ BID).
• Outpatient with Comorbidities / Moderate Risk: Oral Amoxicillin-clavulanate ($875/125\text{ mg}$ BID) or Cefuroxime axetil PLUS a macrolide (Azithromycin), OR respiratory fluoroquinolone monotherapy (Levofloxacin $750\text{ mg}$ or Moxifloxacin $400\text{ mg}$ daily).
• Inpatient Non-Severe (Hospital Ward): Intravenous beta-lactam (Ceftriaxone $1-2\text{ g}$ IV daily, Ampicillin-sulbactam $1.5-3.0\text{ g}$ IV q6h) PLUS intravenous/oral Azithromycin, OR respiratory fluoroquinolone monotherapy.
• Inpatient Severe (ICU): Intravenous non-antipseudomonal beta-lactam (Ceftriaxone or Ampicillin-sulbactam) PLUS intravenous Azithromycin or a respiratory fluoroquinolone. Use an antipseudomonal beta-lactam (Piperacillin-tazobactam $4.5\text{ g}$ IV q6h, Cefepime $2\text{ g}$ IV q8h, or Meropenem $1\text{ g}$ IV q8h) only when risk factors for Pseudomonas are present (structural lung disease such as bronchiectasis, recent hospitalization with IV antibiotics, or prior isolation), and add Vancomycin or Linezolid if MRSA is suspected.

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Pulmonary Tuberculosis & Philippine National TB Control Program (NTP)

The Philippines remains an endemic country for tuberculosis, necessitating standardized programmatic diagnostic pathways and directly observed therapy.

Diagnostic Strategy & Molecular GeneXpert MTB/RIF

• Presumptive TB Definition: Any individual presenting with cough lasting $\ge 2\text{ weeks}$, unexplained fever, night sweats, significant weight loss, hemoptysis, or suspicious chest radiograph lesions.
• Primary Diagnostic Tool: GeneXpert MTB/RIF (or Ultra) is the mandatory initial diagnostic test for all presumptive pulmonary and extrapulmonary TB cases. It utilizes automated real-time PCR to detect Mycobacterium tuberculosis complex DNA and simultaneously identifies mutations in the rpoB gene conferring rifampicin resistance within 2 hours.
• Chest Radiography (CXR): Primary screening examination; reactivation TB classically demonstrates apical and posterior segment infiltrates of upper lobes, with or without cavitation.
• Sputum Smear Microscopy (DSSM): Used primarily for monitoring treatment response in bacteriologically confirmed pulmonary TB: at the end of the intensive phase (month 2), at month 5, and at the end of treatment (month 6).

Standard NTP Treatment Regimens & Drug Mechanisms

• Regimen 1 (Drug-Susceptible Pulmonary and Most Extrapulmonary TB; formerly "Category I"):
  • Intensive Phase (2 Months): 2HRZE — Daily Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), and Ethambutol (E) in Fixed-Dose Combinations (FDC).
  • Continuation Phase (4 Months): 4HR — Daily Isoniazid and Rifampicin.
• Regimen 2 (TB Meningitis and Bone or Joint TB): 2HRZE/10HR, extending the continuation phase to 10 months.

Drug-Induced Liver Injury (DILI) Protocol: Discontinue all hepatotoxic agents (H, R, Z) immediately if serum ALT/AST rises $> 3$ times upper limit of normal with jaundice/hepatitis symptoms, or $> 5$ times upper limit of normal without symptoms. Once enzymes normalize, rechallenge sequentially.

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Acute Respiratory Distress Syndrome (ARDS) & Critical Care

ARDS is acute, diffuse, inflammatory alveolar injury leading to increased vascular permeability, loss of aerated lung tissue, and refractory hypoxemia.

The Berlin Definition of ARDS

1. Timing: Within 1 week of a known clinical insult (sepsis, severe pneumonia, aspiration, pancreatitis, massive trauma) or new/worsening respiratory symptoms.
2. Chest Imaging: Bilateral pulmonary opacities not fully explained by pleural effusions, lobar collapse, or nodules.
3. Origin of Edema: Respiratory failure not fully explained by cardiac failure or hydrostatic volume overload; objective assessment (echocardiography) required to exclude cardiogenic pulmonary edema.
4. Oxygenation Impairment (measured with $\text{PEEP} \ge 5\text{ cm H}_2\text{O}$):
   • Mild ARDS: $200 < \text{PaO}_2/\text{FiO}_2 \le 300\text{ mmHg}$.
   • Moderate ARDS: $100 < \text{PaO}_2/\text{FiO}_2 \le 200\text{ mmHg}$.
   • Severe ARDS: $\text{PaO}_2/\text{FiO}_2 \le 100\text{ mmHg}$.

Evidence-Based Lung-Protective Mechanical Ventilation

• Low Tidal Volume Ventilation: Ventilate with a tidal volume of $4\text{ to }8\text{ mL/kg}$ of Predicted Body Weight (PBW), starting at $6\text{ mL/kg PBW}$ (PBW is calculated from height and sex, NOT actual total body weight). This prevents ventilator-induced lung injury (volutrauma).
• Plateau Pressure Limitation: Maintain inspiratory end-inspiratory plateau airway pressure ($P_{plat}$) $\le 30\text{ cm H}_2\text{O}$ to prevent barotrauma.
• Permissive Hypercapnia: Allow moderate arterial respiratory acidosis ($\text{pH} \ge 7.20-7.25$) to maintain low tidal volumes, provided cerebral perfusion is uncompromised.
• Prone Positioning: Strongly recommended for $\ge 16\text{ consecutive hours per day}$ in patients with moderate-to-severe ARDS ($\text{PaO}_2/\text{FiO}_2 < 150\text{ mmHg}$). Prone ventilation optimizes dorsal alveolar recruitment, balances ventilation-perfusion matching, and significantly reduces 28-day mortality.

More on pneumonia

• Diagnosis: new infiltrate on chest X-ray with symptoms. Sputum Gram stain and culture and blood cultures for admitted patients, plus TB testing when the course is subacute.
• Hospital-acquired and ventilator-associated pneumonia (48 hours or more after admission or intubation): cover Pseudomonas, Klebsiella, Acinetobacter and MRSA based on local data.
• Aspiration pneumonia: stroke, alcohol, seizures and dysphagia. Affects dependent segments (right lower lobe; posterior upper lobe when supine). Lung abscess follows.
• Viral pneumonia: influenza, COVID-19 and RSV. Oseltamivir within 48 hours (or any time in hospitalized and high-risk patients). Watch for secondary S. aureus pneumonia after influenza.
• Melioidosis (Burkholderia pseudomallei): in diabetics after soil and water exposure; pneumonia, abscesses and sepsis, treated with ceftazidime or meropenem.
• Prevention: pneumococcal and influenza vaccination for the elderly and those with chronic disease, and stopping smoking.

More on tuberculosis

• Drug-resistant TB:
  • suspect it after treatment failure, relapse, contact with MDR-TB or rifampicin resistance on Xpert;
  • treated by PMDT facilities with all-oral regimens such as BPaLM (bedaquiline, pretomanid, linezolid, moxifloxacin) for 6 months (WHO 2022), with ECG monitoring for QT prolongation and watching for linezolid neuropathy and myelosuppression.
• Extrapulmonary TB:
  • TB lymphadenitis: the most common form; matted cervical nodes and scrofula;
  • pleural TB: lymphocytic exudate with high ADA;
  • TB meningitis and spinal TB: longer treatment (2HRZE/10HR) with steroids for meningitis.
• TB and HIV: offer HIV testing to all TB patients, and start ART within 2 weeks of TB treatment.
• TB infection (latent TB) and TB preventive treatment:
  • detected by tuberculin skin test or IGRA, after excluding active disease;
  • TB preventive treatment for household contacts (especially children under 5), people living with HIV, and patients starting biologics or dialysis;
  • regimens: 3HP (weekly isoniazid-rifapentine for 3 months), 3HR, or 6H (6 months of isoniazid).
• Case finding: chest X-ray screening and Xpert testing for presumptive TB; treatment support (directly observed or digital) to ensure adherence.

Pulmonary embolism

• Risk factors: recent surgery, immobilization, cancer, pregnancy and estrogen, prior VTE and thrombophilia.
• Presentation: sudden dyspnea, pleuritic chest pain, tachycardia, hypoxia, hemoptysis and syncope. ECG may show sinus tachycardia or the S1Q3T3 pattern (uncommon).
• Diagnosis:
  • Wells score;
  • D-dimer to rule out PE when pretest probability is low;
  • CT pulmonary angiography (V/Q scan in pregnancy or contrast allergy).
• Treatment:
  • anticoagulation with a DOAC or low molecular weight heparin, for at least 3 months;
  • systemic thrombolysis for massive PE with hypotension;
  • an IVC filter only if anticoagulation is contraindicated.

Lung cancer

• Risk factors: smoking (including secondhand), radon, asbestos, biomass smoke and air pollution.
• Types:
  • adenocarcinoma: the most common type; peripheral; also seen in never-smokers, especially Asian women, often with EGFR mutations treated with oral tyrosine kinase inhibitors (osimertinib);
  • squamous cell carcinoma: central, cavitating, linked to smoking, with hypercalcemia from PTHrP;
  • small cell carcinoma: central, aggressive, early spread, linked to SIADH, ectopic ACTH and Lambert-Eaton syndrome; treated with chemotherapy, radiotherapy and immunotherapy.
• Presentation: cough, hemoptysis, weight loss, post-obstructive pneumonia, superior vena cava syndrome (facial swelling, dilated chest veins), Pancoast tumor with Horner syndrome, hoarseness (recurrent laryngeal nerve) and clubbing.
• Workup:
  • CT chest and abdomen;
  • tissue diagnosis by bronchoscopy, CT-guided biopsy or EBUS;
  • molecular testing of adenocarcinoma (EGFR, ALK, PD-L1);
  • staging with PET-CT and brain MRI.
• Screening: low-dose CT yearly for adults aged 50 to 80 with a 20 pack-year smoking history who smoke now or quit within 15 years (USPSTF 2021).
• Prevention: tobacco control (the Graphic Health Warnings Act, sin taxes, smoke-free laws) and cessation support.