LACTOLOGY FOUNDATION

Pleural, hilar, and mediastinal disorders comprise a broad spectrum of inflammatory, structural, neoplastic, and traumatic conditions that share the pleural space and central thoracic compartment as their principal sites of pathology.

Introduction

Disorders of the pleura most commonly present with pleuritic chest pain, pleural effusion, pneumothorax, or chronic pleural thickening, while hilar and mediastinal disease typically manifest as vascular congestion, lymphadenopathy, space‑occupying masses, or acute mediastinitis.
Accurate differentiation of these entities relies on correlation of clinical features with targeted imaging and pleural fluid or tissue analysis, as many conditions present with overlapping symptoms such as chest pain, dyspnea, and radiographic opacities.

Pleuritic Pain and Acute Pleurisy

Pleurisy (pleuritis) is defined as pleural surface inflammation resulting in sharp, inspiratory chest pain originating from the parietal pleura, which is innervated predominantly by intercostal nerves and, over the central diaphragm, by the phrenic nerve.
Pain is typically aggravated by coughing, sneezing, or torso movement, may be referred to the ipsilateral shoulder when diaphragmatic pleura is involved, and must be distinguished from musculoskeletal and pericardial pain by careful examination and auscultation for a pleural friction rub.

In many patients, pleuritic pain is secondary to processes in adjacent lung such as pneumococcal pneumonia that begins peripherally and extends to the pleural surface; others have primary pleural involvement from infection, neoplasm, trauma, or systemic inflammatory disease.
When chest radiography is normal, the differential diagnosis narrows to pulmonary embolism, viral or idiopathic pleurisy, and serositis associated with collagen vascular disease, with less frequent causes including uremia, sickle cell crisis, and Dressler syndrome.

Idiopathic or viral pleuritis is usually self‑limited over several days to two weeks and responds to nonsteroidal anti‑inflammatory drugs, with narcotic analgesia reserved for severe pain, but pulmonary embolism must be rigorously excluded before establishing this diagnosis of exclusion.

Pleural Effusion: Pathophysiology, Classification, and Diagnosis

Pleural effusion represents abnormal accumulation of liquid in the pleural space and is most frequently caused by congestive heart failure, malignancy, pneumonia, and pulmonary embolism.
Seven principal mechanisms favour effusion formation: increased pleural membrane permeability, reduced intravascular oncotic pressure (with secondary rise in pleural oncotic pressure), elevated pleural capillary hydrostatic pressure, increased pleural negative pressure in non‑expanding lung, lymphatic obstruction, transdiaphragmatic passage of ascitic fluid, and migration of pulmonary oedema fluid across the visceral pleura.

Serous effusions (hydrothoraces) are distinguished from haemothorax, chylothorax, and empyema, but definitive classification requires pleural fluid analysis rather than imaging alone.
Transudative hydrothoraces arise from imbalances in hydrostatic and oncotic forces, most commonly heart failure, with other causes including constrictive pericarditis, superior vena cava obstruction, cirrhosis and nephrotic syndrome, while exudates reflect endothelial injury or lymphatic obstruction due to infectious, neoplastic, inflammatory, embolic, vasculitic, drug‑related, or asbestos‑associated disease.

Clinically, effusions produce dullness to percussion, reduced or absent breath sounds, decreased tactile fremitus, and egophony at the fluid meniscus, with chest radiography usually confirming the diagnosis.
Radiographic signs include blunting of the lateral and posterior costophrenic angles (≥25–50 ml), meniscus‑shaped homogeneous opacity displacing lung centrally, complete hemithorax opacification with mediastinal shift in massive effusion, interlobar (pseudotumour) collections in heart failure, subpulmonic effusions altering diaphragmatic contour, and loculation evidenced by oblique margins and atypical densities.

Ultrasonography is highly sensitive for pleural fluid, particularly when loculation is suspected, and guides safe thoracentesis; contrast‑enhanced CT further differentiates pleural masses from loculated effusions and identifies thickened or enhancing parietal pleura in exudates and empyema.
Therapeutic thoracentesis in large effusions should generally be limited to 1,000–1,500 ml per session or terminated when markedly negative pressures are required, in order to reduce the risk of re‑expansion pulmonary oedema in chronically compressed lung.

Routine pleural fluid analysis encompasses macroscopic inspection, total and differential white cell count, red cell count, Gram stain and culture, cytology, pH (by meter), protein, lactate dehydrogenase (LDH), glucose, amylase, and, where appropriate, triglycerides and antinuclear antibody (ANA) titres.
Gross pus or fetid fluid is diagnostic of empyema; very viscous clear fluid suggests mesothelioma through hyaluronic acid production, and “chocolate‑sauce” or “anchovy‑paste” fluid points to hepatopleural fistula from amebiasis.

Four widely used criteria distinguish exudates from transudates more effectively than absolute protein concentration: pleural‑to‑serum protein ratio >0.5, pleural‑to‑serum LDH ratio >0.6, pleural LDH exceeding two‑thirds the serum upper normal limit, or pleural cholesterol ≥60 mg/dl.
If any criterion is fulfilled, the effusion is almost always exudative or due to lymphatic obstruction, whereas failure to meet all four strongly supports a transudative mechanism—although clinical context remains essential because these thresholds are not absolute.

Additional targeted tests refine the aetiology of exudates: elevated amylase indicates pancreatitis, pseudocyst, or malignancy; high red cell counts (>100,000/mm³) suggest malignancy, trauma, or embolism, while a pleural haematocrit >50% of peripheral haematocrit defines haemothorax.
Marked neutrophilia implies acute inflammation from empyema, parapneumonic effusion, pulmonary embolism, pancreatitis, viral pleuritis, or early tuberculosis, whereas small‑lymphocyte predominance in >90% of exudates is associated with malignancy or tuberculous effusion; eosinophilia (>10%) is usually nonspecific and often follows prior introduction of air or blood into the pleural space.

Low pleural pH (<7.3) without systemic acidosis indicates serious exudative processes such as empyema, chronic malignant effusion, collagen vascular disease, tuberculosis, oesophageal rupture, or haemothorax, and pH <7.0 in parapneumonic effusions strongly favours infected pleural space.
Glucose <60 mg/dl occurs in tuberculosis, parapneumonic effusions, empyema, and large malignant effusions due to cellular or microbial consumption, while extremely low glucose in rheumatoid effusions reflects impaired transport across thickened pleura.

ANA titres equal to or greater than serum levels or lupus erythematosus cells support systemic lupus erythematosus as the cause of pleural effusion, whereas rheumatoid factor titres up to 1:160 may be nonspecific and appear in various conditions.
Repeat pleural fluid analysis, closed pleural biopsy, and medical thoracoscopy significantly increase diagnostic yield in suspected tuberculosis or pleural malignancy, with thoracoscopy allowing direct visualisation and biopsy of abnormal pleura.

Specific Pleural Syndromes

Transudative Hydrothorax

In congestive heart failure, pleural effusion is an early manifestation correlated with interstitial pulmonary oedema, often bilateral or right‑sided, and usually resolves within days of effective diuresis and afterload reduction.
Post‑diuretic concentration of protein may shift some effusions into an exudative range by biochemical criteria, but genuinely exudative hydothoraces in heart failure almost always reflect coexisting pathology.

Ascitic fluid from cirrhosis, ovarian tumours, or peritoneal dialysis may traverse diaphragmatic lymphatics or defects to produce hepatic hydrothorax, typically right‑sided in 60–70% of cases.
Management emphasises control of ascites with diuretics or tumour resection, while repeated large‑volume thoracentesis is discouraged due to protein and volume depletion; video‑assisted thoracoscopic closure of diaphragmatic defects may achieve lasting resolution.

Malignant Pleural Effusion and Mesothelioma

Malignant effusions arise from pleural metastases, mediastinal lymphatic obstruction, or primary pleural neoplasms such as diffuse malignant mesothelioma.
Lung and breast cancers predominate as sources of pleural metastases, followed by gastric and ovarian carcinomas, while lymphomas produce effusions mainly through mediastinal nodal infiltration and lymphatic obstruction.

Typical fluid characteristics include serosanguineous appearance, exudative protein and LDH levels, lymphocyte predominance (>50%), normal glucose (>60 mg/dl), and pH >7.3, although these features are not universal.
Massive effusions opacifying an entire hemithorax and effusions resistant to thoracentesis plus closed biopsy strongly suggest malignancy as the underlying cause.

Cytologic examination of pleural fluid with Papanicolaou staining and cell‑block histology yields the diagnosis in most cases, and immunohistochemistry helps distinguish carcinoma, lymphoma, and mesothelioma; diagnostic yield increases with successive thoracenteses.
Image‑guided percutaneous pleural biopsy offers higher sensitivity than blind closed biopsy, while fibreoptic bronchoscopy is reserved for cases with radiographic evidence of bronchogenic carcinoma, and thoracoscopy is required in a minority for definitive diagnosis.

Symptomatic malignant effusions are managed by pleural drainage and, where appropriate, obliteration of the pleural space through chemical pleurodesis.
Small‑bore chest tubes suffice for drainage in many ambulatory patients; after near‑complete evacuation, intrapleural instillation of sclerosing agents such as talc slurry, doxycycline, bleomycin, or iodopovidone induces fibrous adhesion between visceral and parietal pleura.

Talc is inexpensive and as effective as doxycycline or bleomycin, but pleurodesis fails when pleural fluid pH is <7.3 or when the underlying lung cannot re‑expand to fill the thoracic cavity.
Thoracoscopic talc poudrage may achieve superior results compared with bedside pleurodesis, and in refractory cases, long‑term indwelling catheters or pleuroperitoneal shunts provide alternative palliation.

Malignant mesothelioma, strongly linked to asbestos, erionite, and prior radiation exposure, produces diffuse pleural thickening and effusion and carries a poor prognosis despite multimodality therapy.

Tuberculous Hydrothorax

Tuberculous effusions occur more commonly as manifestations of primary rather than reactivation disease, typically arising 3–6 months after initial infection due to rupture of a subpleural focus into the pleural space with subsequent granulomatous involvement of parietal and visceral pleura.
These effusions are usually serous or serosanguineous with lymphocytic predominance, often modestly reduced glucose (<60 mg/dl) and pH (<7.3), and virtually always paucimesothelial (<5% mesothelial cells), with adenosine deaminase and interferon‑gamma levels helpful for differentiation from other causes.

Pleural fluid smear rarely reveals acid‑fast bacilli, and cultures are positive in only 20–40%, but closed pleural biopsy yields granulomas in approximately 70% and positive cultures in 75%, giving a combined diagnostic yield of 90–95%.
Treatment parallels that for pulmonary tuberculosis and requires at least two antituberculous agents for standard durations, without routine need for chest tube drainage except in tuberculous empyema of reactivation disease.

Embolic, Haemorrhagic, and Chylous Effusions

Pulmonary embolism causes pleural effusion in roughly one‑quarter of angiographically documented cases and in more than half of cases diagnosed by spiral CT, through mechanisms likely involving increased capillary permeability and venous hypertension.
Pleural fluid in embolic effusions is often exudative and serosanguineous with neutrophilic predominance, but variability is substantial, and none of the routine analytic parameters reliably excludes embolism.

Haemothorax most commonly follows blunt or penetrating thoracic trauma or iatrogenic vascular injury during procedures, with pleural haematocrit >50% of peripheral haematocrit establishing the diagnosis.
Large or rapidly accumulating haemothoraces require prompt drainage via wide‑bore chest tube, progressing to thoracoscopy or thoracotomy if bleeding ≥100–200 ml/hour persists; undrained blood predisposes to empyema and fibrothorax.

Chylothorax results from thoracic duct disruption or obstruction by lymphomas, metastatic mediastinal tumours, trauma (including thoracic and cardiovascular surgery), lymphangioleiomyomatosis, congenital lymphatic disorders, irradiation, or mediastinal fibrosis.
Chylous effusions appear milky, remain opaque after centrifugation, form a creamy chylomicron layer on standing, clear with ether, and typically have triglycerides >110 mg/dl, while CT identifies underlying mediastinal pathology and cytology occasionally reveals malignant cells.

Because chyle is bacteriostatic, infection is rare, but continuous loss of chyle leads to protein, fat, and lymphocyte depletion with malnutrition and immunosuppression; management therefore combines repeated drainage with specific treatment of the primary cause.
Radiotherapy and chemotherapy address lymphomatous or metastatic disease, thoracic duct ligation or oversewing during thoracotomy cures traumatic leaks, and pleurodesis is reserved for patients who are poor surgical candidates or have refractory malignancy.

Pseudochylothorax (chyliform effusion) mimics chylothorax visually but represents cholesterol crystal accumulation in long‑standing rheumatoid or tuberculous effusions with dense pleural thickening, and treatment is directed at the underlying chronic pleuritis and drainage as needed.

Parapneumonic Effusion and Empyema

Parapneumonic effusions and empyema arise from contiguous spread of infection from pneumonia, lung abscess, bronchiectasis, thoracic surgery, penetrating trauma, subdiaphragmatic sepsis, spontaneous pneumothorax, mediastinitis, or oesophageal rupture.
Causative organisms have shifted over decades from pneumococcus and haemolytic streptococci to Staphylococcus aureus and aerobic Gram‑negative bacilli and, more recently, to mixed anaerobic and aerobic flora and opportunistic fungi in immunocompromised hosts.

Clinically, empyema presents with fever, chest pain, cough, and dyspnoea but may be indolent, especially with anaerobic infection, and up to 15% of patients lack fever or leukocytosis.
Radiographically and by pleural fluid analysis, three categories are recognised: typical parapneumonic effusion with small free fluid, normal glucose and pH, and negative cultures; complicated parapneumonic effusion with larger or loculated fluid, low pH and glucose, high LDH, and positive cultures without overt pus; and empyema with frank pus in single or multiple loculi.

Small effusions (<10 mm thickness on lateral decubitus radiograph) usually resolve with appropriate antibiotics alone and do not require thoracentesis, whereas larger effusions mandate diagnostic aspiration.
Complicated effusions and empyema require tube thoracostomy plus antibiotics, with intrapleural fibrinolytics (streptokinase or urokinase) often facilitating drainage in loculated collections, though evidence of benefit is mixed and urokinase may cause fewer febrile reactions.

Early thoracoscopic intervention is frequently more cost‑effective than prolonged drainage and fibrinolytics in complex empyema, while failure to control infection or achieve drainage necessitates surgical decortication or open window thoracostomy in selected debilitated patients.
Untreated empyema can result in septic shock, empyema necessitatis with chest wall rupture, or bronchopleural fistula.

Chronic Pleural Changes: Plaques, Thickening, Calcification, and Fibrothorax

Pleural plaques are discrete, collagenous, hyalinised thickenings of parietal pleura covered by normal mesothelium, typically on lateral and posterior chest walls and central diaphragm, strongly associated with heavy asbestos exposure and appearing decades after exposure.
They frequently calcify, forming characteristic radiographic opacities, and are clinically significant chiefly as markers of asbestos exposure; lung function impairment is generally minimal.

Diffuse pleural thickening results from fibrotic healing after pleural inflammation due to haemothorax, empyema, tuberculous pleurisy, asbestos, talc, uraemia, or collagen vascular disease.
When extensive, thickening entraps the underlying lung, causing fibrothorax, with substantial restriction of ventilation and gas exchange; once a fibrous peel is organised, only surgical decortication can restore lung expansion in suitable candidates.

Rounded atelectasis is a masslike lesion created by localised pleural fibrosis pulling lung into a rounded configuration, often associated with asbestos‑related thickening and difficult to distinguish radiographically from neoplasm.
Pleural calcification after haemothorax, empyema, or tuberculosis manifests as sheet‑like visceral pleural deposits outlining the inner margin of thickened pleura, mainly at midthoracic levels, in contrast to parietal diaphragmatic calcification in asbestos plaques.

Pneumothorax and Barotrauma

Pneumothorax denotes gas within the pleural space following disruption of visceral or parietal pleura or passage of gas from ruptured intra‑thoracic or abdominal viscera.
Causes include direct chest trauma, diagnostic or therapeutic procedures (thoracentesis, central venous cannulation, intercostal nerve block, acupuncture), focal lesions such as bronchogenic carcinoma, rheumatoid nodules, thoracic endometriosis, necrotising pneumonia, infarction, and diffuse parenchymal diseases like emphysema, asthma, cystic fibrosis, lymphangioleiomyomatosis, and connective‑tissue disorders.

Classification distinguishes traumatic and iatrogenic pneumothorax from spontaneous forms, which are secondary when underlying lung disease is present and idiopathic when no overt pathology is evident aside from subpleural apical blebs and centrilobular emphysema.
Idiopathic spontaneous pneumothorax occurs predominantly in young, tall, thin male smokers, with incidence around 4.3 per 100,000 patient‑years and a 5:1 male‑to‑female ratio, while secondary pneumothorax is common in advanced obstructive lung disease, cystic fibrosis, HIV‑related Pneumocystis pneumonia, eosinophilic granuloma, and lymphangioleiomyomatosis.

Diagnosis relies on acute onset of unilateral pleuritic pain and dyspnoea, physical findings of unilateral hemithorax expansion, hyperresonance, reduced breath sounds, and radiographic demonstration of the visceral pleural line with absent peripheral lung markings.
In supine patients, gas collects anteriorly and basally, producing the deep sulcus sign at the costophrenic angle, and estimation of pneumothorax size uses the approximate correlation of a 1‑inch average gas rim with a 30% collapse.

Management of secondary spontaneous pneumothorax is inherently aggressive, requiring hospitalisation and chest tube drainage even for small collections, and preventive procedures (bleb resection plus pleurodesis) are often recommended after the first episode.
In idiopathic cases, small, minimally symptomatic pneumothoraces may be observed with supplemental oxygen to accelerate resorption, moderate lesions may be aspirated with success in up to 70%, and larger or symptomatic pneumothoraces warrant chest tube placement.

Persistent air leak beyond seven days prompts surgical management via thoracotomy or video‑assisted thoracoscopic surgery, including oversewing or wedge resection of blebs and mechanical or chemical pleurodesis.
Recurrence rates of idiopathic pneumothorax reach 20–50% within five years and increase after each subsequent episode, are higher in women and taller men, and decrease after smoking cessation; most recurrences are ipsilateral despite bilateral blebs.

Tension pneumothorax, a life‑threatening variant where trapped gas accumulates under positive pressure, causes severe dyspnoea, cyanosis, hypotension, mediastinal shift, and diaphragmatic depression and demands immediate decompression via small‑bore catheter or chest tube, often before imaging.
Given its gravity, definitive prophylactic intervention to prevent recurrence is advised after the first tension episode.

Hilar and Mediastinal Disorders

The mediastinum extends from thoracic inlet to diaphragm between sternum and vertebral column and contains heart, great vessels, trachea, main bronchi, oesophagus, thoracic duct, lymph nodes, and autonomic and somatic nerves.
Coronal division into anterior, middle, and posterior compartments assists localisation of masses: the anterior mediastinum houses thymus and fat; the middle includes heart, pericardium, proximal great vessels, central airways, and nodes; the posterior contains descending aorta, oesophagus, thoracic duct, nodes, and sympathetic chain.

Hilar shadows on radiographs represent mainly pulmonary arteries, with the left hilum normally positioned superior and posterior to the right in 97% of individuals; deviation suggests mass effect or lobar collapse.
Hilar enlargement arises from vascular engorgement—due to increased pulmonary blood flow or hypertension—or lymphadenopathy from infection, sarcoidosis, lymphoma, and metastatic carcinoma.

Contrast‑enhanced CT accurately distinguishes vascular from nodal enlargement and characterises nodal morphology, while MRI offers an alternative when iodinated contrast is contraindicated.
Bilateral hilar adenopathy, often with mediastinal involvement, is most commonly sarcoidosis in young to middle‑aged adults, but differential diagnoses include lymphoma, metastatic cancer, chronic granulomatous infection, and berylliosis; clinical features such as systemic symptoms, peripheral nodes, or hepatosplenomegaly help stratify likelihood.

Diagnostic strategies for bilateral hilar adenopathy range from observation or transbronchial lung biopsy in presumed sarcoidosis to mediastinoscopy for suspected lymphoma and PET‑guided needle aspiration for suspected carcinoma.

Acute bacterial mediastinitis usually follows oesophageal rupture (Boerhaave syndrome) or contiguous spread from empyema, lung abscess, pericarditis, or retropharyngeal abscess, and may also complicate median sternotomy or infected bronchogenic cyst.
Patients present with fever, dysphagia, severe chest pain, and radiographic mediastinal widening with possible pneumomediastinum and pleural effusions; management requires broad‑spectrum antibiotics including anaerobic coverage and surgical drainage, with percutaneous catheter drainage reserved for select limited leaks.

Chronic mediastinal widening results mainly from mediastinal lipomatosis in obesity or Cushing states and fibrosing mediastinitis following histoplasmosis or tuberculosis, the latter often causing superior vena cava syndrome and obstruction of major airway or vascular structures.

Anterior mediastinal masses include thymic lesions, teratomas and dermoid cysts, intrathoracic goitre, lymphoma, germ‑cell tumours, and mesenchymal neoplasms.
Thymoma, frequently associated with myasthenia gravis, may be benign or invasive; teratomas and dermoid cysts derive from germ cells and may contain hair, bone, or teeth and occasionally rupture into airways or mediastinum; retrosternal goitre may cause tracheal compression, dysphagia, and vascular compromise and is usually managed surgically.

Middle mediastinal lesions encompass lymphomas, tracheal carcinomas, metastatic nodal disease, granulomatous mediastinitis, bronchogenic and pleuropericardial cysts, Morgagni hernias, Castleman disease, and vascular dilatations.
Bronchogenic cysts near the carina are lined by respiratory epithelium, may communicate with the airway, and warrant excision when infected or symptomatic.

Posterior mediastinum is the site of neurogenic tumours—including schwannomas, ganglioneuromas, neuroblastomas, ganglioneuroblastomas, and neurofibromas—along with neurenteric and enteric cysts, thoracic duct and oesophageal lesions, Bochdalek hernias, spinal disease, and extramedullary haematopoiesis.
Neurogenic tumours may erode ribs, cause pleural effusions, and extend through intervertebral foramina to create dumbbell masses, requiring combined thoracic and neurosurgical management.

Pneumomediastinum

Pneumomediastinum arises when gas enters the mediastinum from ruptured oesophagus or tracheobronchial tree, dissects from cervical or retroperitoneal fascial planes, or tracks from ruptured alveoli along perivascular interstitium, as in barotrauma during mechanical ventilation or bronchoscopy.
Spontaneous pneumomediastinum typically affects young, otherwise healthy individuals after intense respiratory efforts such as labour, cough, emesis, Valsalva manoeuvres, or recreational drug use, and presents with retrosternal pain, dyspnoea, neck swelling, subcutaneous emphysema, and Hamman’s mediastinal crunch.

Radiography shows lucent gas outlining the cardiac silhouette and aortic knob and tracking into the neck, with CT required in subtle cases; treatment is conservative with rest, analgesia, avoidance of strain, and high‑concentration oxygen to enhance nitrogen washout, as recurrence and haemodynamic compromise are rare.