John T. Huggins

Causes and management of pleural fibrosis

Abstract:  The development of pleural fibrosis follows severe pleural space inflammation which is typically associated with an exudative pleural effusion. The response of the mesothelial cell to injury and its ability, along with the basement membrane, to maintain its integrity, is vital in determining whether there is normal healing or pleural fibrosis. The formation of a fibrinous intrapleural matrix is critical to the development of pleural fibrosis. This matrix is the result of disordered fibrin turnover, whereby fibrin formation is up‐regulated and fibrin dissolution is down‐regulated. Cytokines, such as TGF‐β and TNF‐α, facilitate the fibrin matrix formation. A complete understanding of the pathogenesis of pleural fibrosis and why abnormal pleural space remodeling occurs in some and not in others, remains unknown. Clinically significant pleural fibrosis requires involvement of the visceral pleura. Isolated parietal pleural fibrosis, as with asbestos pleural plaques, does not cause restriction or respiratory impairment. The causes of visceral pleural fibrosis include asbestos‐associated diffuse pleural thickening, coronary bypass graft surgery, pleural infection (including tuberculous pleurisy), drug‐induced pleuritis, rheumatoid pleurisy, uraemic pleurisy, and haemothorax. Systemic and intrapleural corticosteroids administered during the initial presentation of rheumatoid pleurisy in small series may decrease the incidence of pleural fibrosis. Several randomised control trials using corticosteroids in tuberculous pleurisy have not shown efficacy in reducing residual pleural fibrosis. Decortication is effective in treating symptomatic patients regardless of the cause of pleural fibrosis as long as chronicity has been documented and significant underlying parenchymal disease has been excluded.

Drug-induced pleural disease

Drug-induced pleural disease is uncommon and less known to clinicians than drug-induced parenchymal lung disease. Pleural reactions from drugs manifest as pleural effusions, pleural thickening, or pleuritic chest pain, and may occur in the absence of parenchymal infiltrates. The clinician should be cognizant of the possibility of a drug-induced pleural reaction. A detailed drug history, temporal relationship between symptom onset and initiation of therapy, and pleural fluid eosinophilia should raise the suspicion of a drug-related process. We suspect that as new drugs are marketed in the United States, the number of drugs that result in pleuropulmonary toxicity will continue to increase. Moreover, if the cause of an exudative pleural effusion is not clinically obvious after pleural fluid analysis, drug therapy withdrawal should be a consideration if clinically appropriate before initiating an extensive diagnostic evaluation that may entail unnecessary economic burden and discomfort for the patient.

Pathophysiology of Pneumothorax Following Ultrasound-Guided Thoracentesis

STUDY OBJECTIVES Pneumothorax following ultrasound-guided thoracentesis is rare. Our goal was to explain the mechanisms of pneumothorax following ultrasound-guided thoracentesis in a setting where pleural manometry is routinely used. METHODS We reviewed the patient records and procedure reports of 401 patients who underwent ultrasound-guided thoracentesis. When manometry was performed, pleural space elastance was determined. A model assuming dependence of the pleural space elastic properties on respiratory system elastic properties was used to isolate cases with presumed normal pleural space elastance. Elastance outside mean +/- SD x 2 of the isolated sample was considered abnormal. Four radiographic criteria of unexpandable lung were used: visceral pleural peel, lobar atelectasis, basilar pneumothorax, and pneumothorax with ipsilateral shift. RESULTS There were 102 diagnostic thoracenteses, 192 therapeutic thoracenteses with pleural manometry, and 73 therapeutic thoracenteses without manometry. There was one pneumothorax that occurred from lung puncture and eight unintentional pneumothoraces, all of which showed radiographic evidence of unexpandable lung. Four of eight unintentional pneumothoraces had abnormal elastance; none had excessively negative pleural pressure (< -25 cm H(2)O). CONCLUSIONS Unintentional pneumothoraces cannot be prevented by monitoring for symptoms or excessively negative pressure. These pneumothoraces were drainage related rather than due to penetrating lung trauma or external air introduction. We speculate that unintentional pneumothoraces are caused by transient, parenchymal-pleural fistulae caused by nonuniform stress distribution over the visceral pleura that develop during large-volume drainage if the lung cannot conform to the shape of the thoracic cavity in some patients with unexpandable lung. These fistulae appear to be pressure dependent, and the resulting pneumothoraces rarely require treatment. Drainage-related pneumothorax is an unavoidable complication of ultrasound-guided thoracentesis and appears to account for the vast majority of pneumothoraces occurring in a procedure service.

The unexpandable lung

Unexpandable lung is the inability of the lung to expand to the chest wall allowing for normal visceral and parietal pleural apposition. It is the direct result of either pleural disease, endobronchial obstruction resulting in lobar collapse, or chronic atelectasis. Unexpandable lung occurring as a consequence of active or remote pleural disease may present as a post-thoracentesis hydropneumothorax or an effusion that cannot be completely drained because of the development of anterior chest pain. Pleural manometry is useful for identifying unexpandable lung during initial pleural drainage. Unexpandable lung occurring as a consequence of active or remote pleural disease may be separated into two distinct clinical entities termed trapped lung and lung entrapment. Trapped lung is a diagnosis proper and is caused by the formation of a fibrous visceral pleural peel (in the absence of malignancy or active pleural inflammation). The mechanical effect of the pleural peel constitutes the primary clinical problem. Lung entrapment may result from a visceral pleural peel secondary to active pleural inflammation, infection, or malignancy. In these cases, the underlying malignant or inflammatory condition is the primary clinical problem, which may or may not be complicated by unexpandable lung due to visceral pleural involvement. The recognition of trapped lung and lung entrapment as related, but distinct, clinical entities has direct consequences on clinical management. In our practice, pleural manometry is routinely performed during therapeutic thoracentesis and is useful for identification of unexpandable lung and has allowed us to understand the mechanisms surrounding a post-thoracentesis pneumothorax.

Duro-Pleural Fistula Diagnosed by β2-Transferrin

An 81-year-old man was referred for evaluation of a chronic transudative pleural effusion that required 8 therapeutic thoracenteses over 11 months for relief of dyspnea. Extensive lumbar disk surgery had been performed 2 years prior to his onset of dyspnea. The diagnosis of duro-pleural fistula was confirmed by finding the presence of β2-transferrin in the pleural fluid. The ‘water-like’ pleural fluid had a total protein of <1 gm/dl, an LDH of 92 IU/l, a glucose of 101 mg/dl, and pH of 7.55. β2-Transferrin has a sensitivity approaching 100% and a specificity of 95% in identifying CSF leaks from head trauma. To our knowledge, this is the first report of β2-transferrin in pleural fluid from a duro-pleural fistula.

Can tuberculous pleural effusions be diagnosed by pleural fluid analysis alone

OBJECTIVE To assess whether pleural fluid analysis (PFA) can confidently diagnose tuberculous pleural effusion (TPE). METHODS PFA of 548 TPEs was performed between January 1991 and December 2011. The control group consisted of patients with malignant PE (MPE), complicated parapneumonic/empyema (infectious) PE (IPE), miscellaneous PE (MisPE) and transudative PE (TrPE). RESULTS The PFA of 548 histologically or culture-positive consecutive cases of TPE was compared with that of 158 consecutive cases of MPE, 113 cases of IPE, 37 cases of MisPE and 115 cases of TrPE. Statistically significant differences were noted in pleural fluid glucose, pH, cholesterol, triglycerides, adenosine deaminase (ADA), and total percentages of lymphocytes, neutrophils and macrophages when TPEs were compared to all other groups. Of the TPEs, 99.1% were exudates. Pleural fluid protein ≥ 5.0 g/dl, lymphocytes > 80% and ADA > 45 U/l were diagnostic of TPE, with a specificity of 100%, a sensitivity of 34.9% and an area under the curve of 0.975. CONCLUSION PFA alone was diagnostic in one third of the TPE cases, with a high probability in nearly 60%.

Characteristics of patients with yellow nail syndrome and pleural effusion

Yellow nail syndrome (YNS) can be associated with a pleural effusion (PE) but the characteristics of these patients are not well defined. We performed a systematic review across four electronic databases for studies reporting clinical findings, PE characteristics, and most effective treatment of YNS. Case descriptions and retrospective studies were included, unrestricted by year of publication. We reviewed 112 studies (150 patients), spanning a period of nearly 50 years. The male/female ratio was 1.2/1. The median age was 60 years (range: 0–88). Seventy‐eight percent were between 41–80 years old. All cases had lymphoedema and 85.6% had yellow nails. PEs were bilateral in 68.3%. The appearance of the fluid was serous in 75.3%, milky in 22.3% and purulent in 3.5%. The PE was an exudate in 94.7% with lymphocytic predominance in 96% with a low count of nucleated cells. In 61 of 66 (92.4%) of patients, pleural fluid protein values were >3 g/dL, and typically higher than pleural fluid LDH. Pleurodesis and decortication/pleurectomy were effective in 81.8% and 88.9% of cases, respectively, in the treatment of symptomatic PEs. The development of YNS and PE occurs between the fifth to eighth decade of life and is associated with lymphoedema. The PE is usually bilateral and behaves as a lymphocyte‐predominant exudate. The most effective treatments appear to be pleurodesis and decortication/pleurectomy.

Eucalyptus as a specific irritant causing vocal cord dysfunction

BACKGROUND Vocal cord dysfunction (VCD) is a well-recognized clinical entity that frequently mimics asthma and is characterized by inappropriate adduction of the vocal cords during inspiration. The pathogenesis of VCD has not yet been defined. The only previous report suggested that respiratory irritants may trigger paradoxical motion of the vocal cords. OBJECTIVE To report the case of a 46-year-old woman with VCD precipitated by eucalyptus exposure. METHODS A masked flexible fiberoptic nasolaryngoscopy was performed to confirm whether VCD occurred with eucalyptus and not with other known respiratory irritants. The patient underwent inhalation challenges consisting of water, ammonia, pine oil, and a combination of eucalyptus (dried leaves) and ammonia. Two independent observers before patient challenge could not identify eucalyptus. RESULTS Vocal cord dysfunction occurred within minutes of exposure to eucalyptus. This is the first report to prospectively document that a specific irritant, eucalyptus, can precipitate VCD. Negative skin prick test results, total IgE level, and negative IgE eucalyptus-specific antibodies support a nonimmunologic mechanism. CONCLUSIONS A new pathogenic mechanism for this clinical entity is supported by our observations. Furthermore, a nonimmunologic mechanism in which respiratory irritants may induce VCD is suspected. Future studies to elucidate this mechanism need to be performed in individuals with irritant-specific VCD.

Parasitic Diseases of the Pleura

Abstract:Parasitic infections are prevalent in certain parts of the world and may cause pleural involvement, which often goes unrecognized. Common parasites involving the pleura include Entamoeba histolytica, Echinococcus granulosus and Paragonimus westermani. Amebiasis can cause empyema with “anchovy sauce” pus, reactive pleural effusions and bronchopleural fistula with hydropneumothorax. Echinococcosis may result in pleural thickening, pneumothorax, secondary pleural hydatidosis and pleural effusions. Paragonimiasis may cause chylous and cholesterol pleural effusions, pleural thickening and pneumothorax. Less commonly, pulmonary eosinophilia, or Loefflers syndrome, caused by Ascaris lumbricoides, Ancylostoma duodenale and Necator americanus and tropical pulmonary eosinophilia caused by Wuchereria bancrofti and Brugia malayi may involve the pleura. This article provides a comprehensive review of parasitic infections involving the pleura. A high index of suspicion in the appropriate clinical setting is required to facilitate prompt diagnosis and treatment of these diseases.

The accuracy of pleural ultrasonography in diagnosing complicated parapneumonic pleural effusions

We compared the accuracy of pleural ultrasound versus chest CT versus chest radiograph (CXR) to determine radiographic complexity in predicting a complicated parapneumonic effusion (CPPE) defined by pleural fluid analysis. 66 patients with parapneumonic effusions were identified with complete data. Pleural ultrasound had a sensitivity of 69.2% (95% CI 48.2% to 85.7%) and specificity of 90.0% (95% CI 76.3% to 97.2%). Chest CT had a sensitivity of 76.9% (95% CI 56.3% to 91.0%) and specificity of 65.0% (95% CI 48.3% to 79.4%). CXR had a sensitivity of 61.5% (95% CI 40.6% to 79.8%) and specificity of 60.0% (95% CI 43.3% to 75.1%). Pleural ultrasound appears to be a superior modality to rule in a CPPE when compared with chest CT and CXR.