N-Acetylcysteine (NAC)

N-acetylcysteine (NAC) can help with whooping cough (pertussis) mainly as a mucolytic/airway-clearing and anti-inflammatory/antioxidant agent — it is supportive/symptomatic care, not an established curative or first-line antimicrobial for Bordetella pertussis. High-quality evidence that NAC shortens the course of pertussis is sparse — most authoritative guidance still recommends macrolide antibiotics and supportive care; the NAC literature for pertussis is limited to case reports and extrapolation from other respiratory diseases.

Mucolytic action (primary rationale): NAC breaks disulfide bonds in mucoproteins, lowering mucus viscosity and helping expectoration/clearance of thick secretions. In pertussis the paroxysmal cough and airway obstruction are often worsened by tenacious mucus, so a mucolytic can improve airway clearance. SAGE Journals

Antioxidant / anti-inflammatory effects (secondary rationale): NAC is a cysteine donor and precursor of glutathione; it reduces oxidative stress and can blunt inflammation in the airway, which may reduce tissue injury and help recovery from severe inflammation-associated respiratory failure. This is why NAC has been studied in acute respiratory illnesses and in some chronic airway diseases. Nutritional Medicine Institute

Clinical niche in pertussis: Because antibiotics (macrolides) treat or prevent transmission but often do not shorten the prolonged non-infectious paroxysmal cough once it’s established, therapies that improve mucus clearance are attractive as symptomatic treatments. However, that attraction is mechanistic/physiological rather than proven by strong randomized trials in pertussis. CDC

Inhalation/nebulised solution (most common for airway mucus):

• Usual nebuliser doses reported in prescribing literature: 3–5 mL of a 20% solution (i.e. 200 mg/mL) or 6–10 mL of a 10% solution (100 mg/mL), given 3–4 times daily. Some sources give a broader range (1–10 mL 10% or 2–5 mL 20% frequency 3–4×/day); hospitals will titrate by effect and tolerance. Nebulised NAC is often preceded by a bronchodilator in patients with bronchospasm risk. Empr

Oral NAC (mucolytic formulations):

• In some countries oral effervescent acetylcysteine tablets (e.g. 600 mg) are used for chronic sputum-producing conditions; manufacturers and national formularies give guidance (e.g., single 600 mg effervescent tablet daily in some COPD guidance). Oral use is intended for systemically augmenting glutathione and mucolysis from the airway surface; its onset for acute mucous plugging is slower than inhaled therapy. NICE

Direct instillation during bronchoscopy (rescue therapy in severe cases):

• There are case reports of bronchoscopic instillation (lavage) of NAC to remove thick inspissated secretions in infants with life-threatening pertussis and respiratory failure — this is an invasive, hospital-only rescue measure (performed alongside airway suctioning/ventilator support). Dosing in these reports is procedure-specific and performed by specialists; it is not a routine bedside treatment. Pediatrics

Practical points for use in pertussis

• Who would get NAC? Typically patients with significant mucus plugging or very thick secretions impairing ventilation — often in hospital. For the usual outpatient paroxysmal cough, evidence is weak and clinicians vary. Guidelines emphasize macrolide antibiotics for infection control; NAC is an adjunct for symptom management when indicated. CDC
• Administration tips: Nebulised NAC can provoke bronchospasm in susceptible patients — give a bronchodilator beforehand if the patient has reactive airways; dilute/prepare exactly per product instructions; use sterile diluent and discard diluted doses within the recommended time window. Hospital staff perform instillation and suctioning during bronchoscopy; families should not attempt bronchoscopy-level procedures at home. Boehringer Ingelheim

• There are no large randomized controlled trials showing NAC cures or shortens classical pertussis. High-quality evidence specific to pertussis is lacking. Most authoritative reviews of pertussis management focus on antibiotics (macrolides) and supportive care; cough-specific therapies have mixed or insufficient evidence. CDC
• Case reports / series (level = low evidence):
• Example: Bronchoscopy with N-acetylcysteine lavage in severe respiratory failure due to pertussis — a report of repeated bronchoscopic NAC instillations helping a critically ill infant with pertussis and severe airway obstruction. This shows a possible rescue role in severe, life-threatening mucus plugging but is not generalizable. Pediatrics
• Indirect evidence from other respiratory illnesses: NAC’s mucolytic, antioxidant and anti-inflammatory benefits are supported by RCTs and systematic reviews for other conditions (COPD, bronchiectasis, some viral RTIs) — these data support plausibility but do not prove efficacy specifically for pertussis. Systematic reviews/cochrane work on mucolytics for acute RTIs in children show limited or inconsistent benefits and call for caution. BMJ Open
• Research reviews on pertussis therapies: Reviews on novel therapies for pertussis discuss host-directed therapies and symptomatic interventions, but they do not identify NAC as an evidence-based standard therapy for routine use in pertussis. Oxford Academic

Summary: Mechanistically plausible and used as supportive therapy; clinical proof in pertussis is limited to low-level evidence (case reports) and extrapolation from other respiratory diseases. NAC should not replace macrolide therapy or standard supportive care; its role is adjunctive and case-dependent.