What is the differential diagnosis for a patient with a 2-month history of cough, recent onset of shortness of breath (SOB) since 3 days, and gradual onset of altered sensorium since 1 day, with a past history of Cerebrovascular Accident (CVA)?

Differential Diagnosis for Chronic Cough with Acute Respiratory Decompensation and Altered Sensorium

This patient requires immediate evaluation for aspiration pneumonia given the combination of chronic cough, acute shortness of breath, altered mental status, and prior CVA history, as aspiration is a critical life-threatening condition in stroke survivors with dysphagia.

Primary Diagnostic Considerations

Aspiration Pneumonia (Highest Priority)

• Patients with prior CVA are at markedly elevated risk for aspiration due to oral-pharyngeal dysphagia, with witnessed aspiration and sedative medications identified as the most important risk factors for pneumonia 1
• The 2-month cough may represent chronic microaspiration, with the acute SOB indicating progression to frank aspiration pneumonia 1
• Altered sensorium in this context suggests either severe hypoxemia from pneumonia or a recurrent CVA, both of which increase aspiration risk 1
• Critically, aspiration can occur without coughing (silent aspiration), so the presence of chronic cough does not exclude this diagnosis 1
• Bed-bound status, reduced activity levels, and dependence on others for feeding are strongly associated with aspiration pneumonia (OR 3.03 for gastric tube feeding, OR 2.8 for requiring total assistance with oral care) 1

Recurrent Cerebrovascular Accident

• The gradual onset altered sensorium over 1 day in a patient with prior CVA history mandates urgent neuroimaging to exclude stroke recurrence 2
• Altered sensorium was the presenting symptom in 54.5% of patients with cerebral venous sinus thrombosis, which can present with non-specific neurological symptoms 2
• A new CVA would further compromise swallowing function and increase aspiration risk 1

Postinfectious Cough with Secondary Bacterial Infection

• Postinfectious cough typically presents as persistent dry cough in previously healthy persons where all other symptoms of the inciting upper respiratory tract infection resolved weeks or months earlier 1
• The 2-month duration fits the timeline for postinfectious cough, which may have transient viral-induced bronchial hyperresponsiveness 1
• The acute SOB over 3 days suggests secondary bacterial pneumonia superimposed on chronic cough 3

Cough-Variant Asthma (CVA)

• Asthma accounts for 24-29% of chronic cough cases in adult nonsmokers, and CVA presents with cough as the predominant or sole symptom without wheezing or dyspnea 1
• However, the acute SOB development suggests either progression to typical asthma or a superimposed process 1
• Physical examination and pulmonary function tests can be entirely normal in CVA, requiring methacholine challenge testing for diagnosis 1
• The altered sensorium is not explained by CVA alone and suggests a concurrent serious process 4

Pertussis (Bordetella pertussis)

• When cough lasts >2 weeks without another apparent cause and is accompanied by paroxysms, post-tussive vomiting, and/or inspiratory whooping, pertussis should be diagnosed unless proven otherwise 1
• Pertussis remains highly contagious with secondary attack rates exceeding 80% among susceptible persons 5
• The absence of fever with paroxysmal cough is characteristic of pertussis 6
• However, pertussis does not explain the altered sensorium 1

Critical Red Flag Assessment

Immediate Life-Threatening Conditions to Exclude

• Hemoptysis, hoarseness persisting with cough, recurrent pneumonia, digital clubbing, and dysphagia are red flag symptoms requiring immediate evaluation 6
• The altered sensorium itself is a red flag indicating either severe hypoxemia, sepsis, or intracranial pathology 2, 7
• In patients with prior CVA, specifically assess for dysphagia as it dramatically increases pneumonia risk 1

Neurological Complications

• Meningoencephalitis with bilateral pneumonia can present with fever, cough, shortness of breath, lethargy, and confusion, with rapidly worsening clinical course 7
• Cerebral venous sinus thrombosis should be considered, particularly given the high mortality rate (36.4%) and female predominance 2

Diagnostic Approach Algorithm

Step 1: Immediate Stabilization and Assessment (First Hour)

• Assess oxygenation status and provide supplemental oxygen as needed 3, 8
• Obtain vital signs including temperature, respiratory rate, oxygen saturation 7
• Perform neurological examination with Glasgow Coma Scale to quantify altered sensorium 2
• Assess for signs of aspiration: wet/gurgly voice quality, coughing during or after swallowing attempts 1

Step 2: Urgent Diagnostic Testing (First 4-6 Hours)

• Chest radiograph to evaluate for pneumonia, with particular attention to dependent lung zones where aspiration typically occurs 3, 7
• Urgent brain CT or MRI to exclude acute CVA given altered sensorium and prior stroke history 2
• Complete blood count, metabolic panel, arterial blood gas if hypoxemic 8, 7
• Blood cultures if febrile or septic 7
• Sputum culture if productive cough present 8

Step 3: Targeted History (Concurrent with Above)

• Specifically assess for paroxysmal cough, post-tussive vomiting, and inspiratory whooping sound to evaluate for pertussis 1, 6
• Question patient/caregivers about coughing while eating and drinking, as subjective reports have 74% sensitivity and 74% specificity for aspiration 1
• Assess for constitutional symptoms: fever, weight loss, night sweats (tuberculosis consideration in endemic areas) 6, 8
• Medication review, particularly for ACE inhibitors which can cause chronic cough 9
• Smoking history, as 90% of chronic bronchitis patients have cough resolution after cessation 9

Step 4: Specialized Testing Based on Initial Results

• If aspiration suspected: videofluoroscopic swallow evaluation (VSE) or fiberoptic endoscopic evaluation of swallowing (FEES) once stabilized 1
• If CVA suspected: methacholine inhalation challenge testing to document bronchial hyperresponsiveness, though diagnosis requires documented cough resolution with antiasthmatic therapy 1
• If pertussis suspected: nasopharyngeal aspirate or Dacron swab for culture (gold standard), with PCR if available 1
• If postinfectious cough suspected: consider empiric trial of inhaled bronchodilators and corticosteroids 1

Common Pitfalls to Avoid

• Do not assume cough presence excludes aspiration; silent aspiration occurs frequently in stroke patients 1
• Do not delay neuroimaging in altered sensorium patients with CVA history, as recurrent stroke dramatically worsens prognosis 2
• Do not rely on normal spirometry to exclude CVA, as physical examination and pulmonary function tests can be entirely normal 1
• Do not wait for culture confirmation before treating suspected pertussis; therapy should begin immediately as early treatment during the catarrhal phase decreases complications 1
• Multiple conditions frequently coexist in chronic cough patients; systematically evaluate upper airway cough syndrome, asthma, and GERD as these commonly contribute simultaneously 9

Initial Management Priorities

Immediate Interventions

• Ensure airway protection given altered sensorium and aspiration risk 8, 7
• NPO status until swallowing safety assessed in patient with prior CVA 1
• Broad-spectrum antibiotics if aspiration pneumonia suspected, covering anaerobes 7
• Anticoagulation consideration if CVA or cerebral venous thrombosis identified 2

Empiric Treatment Considerations

• If pertussis suspected, initiate erythromycin 1-2g daily for adults or azithromycin immediately without waiting for confirmation, with isolation for 5 days after therapy starts 1, 5
• If CVA suspected after excluding other causes, initiate inhaled bronchodilators and inhaled corticosteroids, expecting partial improvement after 1 week but complete resolution requiring up to 8 weeks 1
• If postinfectious cough likely, consider empiric bronchodilator trial 1