Secondary spontaneous pneumothorax due to extensive pulmonary tuberculosis in a patient with acute hepatitis B flare: clinical challenges and therapeutic decision making—a case report

Introduction

Secondary spontaneous pneumothorax (SSP) is a serious clinical condition characterized by the presence of air in the pleural space in the setting of preexisting pulmonary disease. SSP is more frequently encountered in older individuals with multiple comorbidities and is associated with substantial morbidity, mortality, and a high recurrence rate—estimated at 40%–56% after the first episode. Consequently, optimal management requires an aggressive and comprehensive therapeutic approach. ¹

Pulmonary tuberculosis (TB) is a major global cause of SSP, particularly in countries with a high TB burden. ² Vietnam remains among the 30 high-burden countries for TB and drug-resistant TB, according to the World Health Organization. ³ SSP is a recognized complication of pulmonary TB, most often occurring in cases of extensive or advanced disease. ⁴ Reported incidence rates vary: earlier studies estimate that 1.3%–5% of pulmonary TB cases develop SSP, ⁵ whereas more recent data suggest a frequency of approximately 1%–2% among active TB cases. ⁶ The pathogenesis typically involves destruction of lung parenchyma and rupture of tuberculous cavities or caseous foci adjacent to the visceral pleura, resulting in the formation of a bronchopleural fistula (BPF). The presence of BPF predisposes to persistent pneumothorax, delayed resolution, and potential progression to pyopneumothorax, significantly complicating management and increasing mortality risk. ⁷

Standard management of tuberculous pneumothorax consists of urgent tube thoracostomy to achieve pleural decompression and lung re-expansion, accompanied by prompt initiation of effective anti-tuberculosis therapy. However, persistent air leak (PAL)—generally defined as an air leak persisting beyond 5–7 days after chest tube placement—is a common complication in TB-associated SSP and represents a formal indication for definitive surgical intervention. ⁴ International guidelines identify video-assisted thoracoscopic surgery (VATS) with pleurodesis or blebectomy as the gold standard for closing air fistulas, facilitating lung re-expansion, and minimizing recurrence risk. ⁸

Management becomes particularly challenging in complex cases where persistent PAL occurs in patients with significant comorbidities that markedly elevate surgical risk. In such situations, determining whether to proceed with invasive surgical repair or pursue conservative medical management remains a difficult and highly individualized clinical decision. ⁹

This study adhered to the guidelines outlined in the CARE statement (Supplemental Material). ¹⁰

Case presentation

A 28-year-old male information technology worker, with a known history of chronic hepatitis B diagnosed at 2 years of age and previously without indication for antiviral therapy, presented with progressive respiratory and constitutional symptoms. Four months prior to hospitalization, he developed a cough with cloudy sputum, evening fevers with chills, and night sweats. He self-medicated at home for a presumed upper respiratory infection; however, his symptoms progressively worsened. Over this period, he experienced significant clinical decline, including unintentional weight loss of 15 kg (BMI reduced from 28.7 to 24.1 kg/m²), increasing dyspnea on exertion, generalized fatigue, and anorexia.

He later sought evaluation at a private hospital, where he was diagnosed with bilateral pulmonary tuberculosis, AFB-positive smear, and a flare of chronic hepatitis B. He was subsequently referred to his local TB treatment facility and initiated on the standard RHZE regimen under the national tuberculosis control program, along with Tenofovir 300 mg/day. Despite treatment, his dyspnea and fatigue continued to worsen, prompting further evaluation and hospital admission to the Department of Respiratory Medicine, Military Hospital 175.

At admission, the patient appeared severely infected and markedly cachectic. He exhibited moderate respiratory distress with a respiratory rate of 24 breaths/min, a shallow breathing pattern, mild use of accessory respiratory muscles, and decreased right-sided chest expansion. Oxygen saturation was 94% on room air. Physical examination revealed Galliard’s triad on the right hemithorax and scattered crackles throughout both lung fields.

Chest radiography and computed tomography demonstrated a large right-sided pneumothorax with passive collapse of adjacent lung parenchyma. Extensive bilateral pulmonary disease was noted, including multiple areas of consolidation with heterogeneous density, cavitary destruction, and diffuse bronchiectasis in tubular, saccular, and tree-in-bud patterns, most prominent in both upper lobes (Figure 1).

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Figure 1.

Chest X-ray and CT images from the patient’s initial hospitalization (a) Chest X-ray at admission showing diffuse bilateral consolidations with a right-sided pneumothorax. (b and c) Chest CT scans at admission demonstrating extensive bilateral consolidation, left-sided parenchymal destruction with cavitation, and a right pneumothorax causing compressive collapse of the adjacent lung.

Laboratory evaluation on admission showed: WBC 9.4 G/L, RBC 4.11 T/L, hemoglobin 120 g/L, prothrombin 78.9%, CRP 97.2 mg/L, AST/ALT 400/194.8 U/L, total bilirubin 21.22 µmol/L (direct bilirubin 7.57 µmol/L), albumin 29.7 g/L, and ammonia 20.8 µmol/L. Microbiological testing revealed a negative rapid HIV antibody test, AFB smear 3+, highly positive Xpert MTB/RIF without rifampicin resistance, and an HBV viral load of 1.24 × 10⁵ IU/mL.

A final diagnosis was established: extensive infiltrative pulmonary tuberculosis with destructive bilateral involvement, newly diagnosed TB, AFB-positive, complicated by severe right-sided secondary spontaneous pneumothorax and a severe flare of chronic hepatitis B.

Given marked hepatic dysfunction, the standard first-line anti-TB regimen was discontinued, and an individualized, hepatosparing regimen was initiated, consisting of imipenem/cilastatin, levofloxacin, ethambutol, and linezolid, with continuation of Tenofovir 300 mg/day. Intensive liver-supportive therapy was provided. Because of his poor functional status and absence of acute respiratory failure, only needle aspiration of pleural air was performed. Supplemental oxygen at 3 L/min was administered, maintaining SpO₂ ⩾ 95%.

After 1 week of treatment, the patient’s hepatic function demonstrated a clear and favorable trend. Liver enzymes normalized (AST/ALT 25.1/45.6 IU/L), and bilirubin levels decreased (total/direct bilirubin 12.34/2.72 µmol/L). However, his respiratory status deteriorated, with increasing dyspnea and signs of impending respiratory failure. He exhibited rapid, shallow breathing at 28 breaths/min and required 6 L/min supplemental oxygen to maintain SpO₂ of only 90%–92%. Arterial blood gas analysis revealed PaO₂ 24.4 mmHg, PaCO₂ 43.9 mmHg, pH 7.398, and HCO₃⁻ 26.5 mmol/L. Chest radiography and CT imaging indicated progression of the right-sided pneumothorax (Figure 2).

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Figure 2.

Chest X-ray and CT imaging performed one week after admission. (a) X-ray showing an increase in the size of the right-sided pneumothorax. (b and c) Chest CT scans demonstrating progression of the right pneumothorax.

Given the acute respiratory compromise and risk of hemodynamic instability, an emergency right-sided tube thoracostomy was performed using a 24F Argyle chest tube. Following drainage, the patient experienced substantial symptomatic relief, with SpO₂ improving to 97% on 3 L/min supplemental oxygen and respiratory rate decreasing to 22 breaths/min. With stabilization of hepatic enzymes and overall liver function, standard first-line anti-tuberculosis therapy was reintroduced, including rifampicin, isoniazid, ethambutol, and pyrazinamide.

Despite appropriate tube placement, PAL continued over 5 days, with no radiological evidence of improvement. After multidisciplinary consultation, chemical pleurodesis with povidone-iodine (Betadine) was performed, combined with continuous negative-pressure suction at −15 cmH₂O. Serial chest radiographs on days 2 and 5 post-pleurodesis showed partial improvement in the pneumothorax; however, complete re-expansion of the right lung was not achieved (Figure 3). Clinically, the patient remained stable, reporting no dyspnea at rest and maintaining an SpO₂ of 97% on room air. To minimize the risk of pleural infection and given evidence of a chronic air leak, continued drainage was unlikely to provide additional clinical benefit; therefore, the chest tube was removed on day 10. In the subsequent days, the patient’s respiratory status remained stable. He was discharged home with instructions to continue oxygen therapy as needed and to adhere to both anti-tuberculosis and hepatitis B treatment regimens.

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Figure 3.

Chest X-ray 24 h after right-sided pleurodesis: showing partial reduction of the pneumothorax.

Seven days after discharge, the patient returned for follow-up in a state of marked fatigue, mild dyspnea, and reduced exercise tolerance, accompanied by obvious signs of obstructive jaundice. Laboratory testing revealed significant hepatic dysfunction, with total/direct bilirubin levels of 54.2/31.39 µmol/L and markedly elevated AST and ALT. Chest radiography and CT imaging demonstrated worsening pneumothorax with near-total collapse of the right lung (Figure 4). Notably, despite the severe radiologic findings, the patient remained clinically stable, presenting with only mild dyspnea, reduced exercise capacity, a respiratory rate of 18 breaths/min, SpO₂ of 96% on room air, and no fever, cough, or sputum production.

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Figure 4.

Chest X-ray and CT images from the patient’s second hospitalization: Chest X-ray and CT scans demonstrating a large recurrent right-sided pneumothorax.

Following multidisciplinary consultation, the clinical team elected to continue conservative medical management rather than pursue further pleural intervention or thoracic surgery, given the high surgical risk in the context of acute liver failure. The patient received intensive hepatoprotective therapy, supplemental oxygen via nasal cannula to maintain SpO₂ at 99%–100%, and adjustments to his anti-tuberculosis regimen. Treatment was modified to rifampicin, ethambutol, levofloxacin, and linezolid, in combination with active liver detoxification and supportive care. After 1 week, liver function improved significantly, and the patient was discharged to continue the adjusted regimen at home.

At the 1-month follow-up, the patient was clinically stable. He reported no dyspnea or infectious symptoms, complete resolution of jaundice, and a weight gain of 2 kg. The modified anti-tuberculosis regimen was well tolerated. Laboratory tests showed normalization of liver enzymes and bilirubin levels, sputum acid-fast bacilli smear was negative, and chest CT demonstrated a reduction in right pleural air with progressive absorption of isodense parenchymal lesions. The patient was advised to continue the current anti-tuberculosis regimen with routine follow-up.

After 3 months of treatment, the patient remained clinically stable with marked improvement in respiratory symptoms. Imaging revealed further resolution of the pneumothorax, substantial absorption of parenchymal lesions, and the development of fibrotic changes.

At completion of 6 months of anti-tuberculosis therapy, the patient had gained a total of 17 kg, maintained normal liver function, and chest CT confirmed complete reabsorption of the right-sided pleural air with residual fibrotic remodeling. Serial chest CT scans obtained at 1, 3, and 6 months after initiation of therapy demonstrated progressive improvement in lung parenchymal lesions and resolution of the pneumothorax (Figure 5). The patient returned to normal daily activities and resumed work without limitations. The patient’s entire treatment course over time is summarized in a flowchart (Figure 6).

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Figure 5.

Serial chest CT images after anti-tuberculosis treatment at 1, 3, and 6 months: (a) 1 month, (b) 3 months, and (c) 6 months.

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Figure 6.

Flowchart illustrating the patient’s disease progression and treatment course.

Discussion

SSP is a challenging clinical condition, particularly when caused by active pulmonary tuberculosis. The present case exemplifies the difficulty of managing SSP in a patient with extensive TB-related lung destruction and severe comorbidities requiring individualized, non-standard treatment.

TB-associated SSP is uncommon but serious, occurring in approximately 0.6%–1.4% of pulmonary TB cases. Compared with primary pneumothorax, SSP carries a poorer prognosis, with recurrence rates of 40%–56% when treated conservatively.^11,12 In tuberculosis, this risk is amplified by parenchymal destruction and BPF, which predispose to PAL and delayed healing. Thus, international guidelines recommend early chest tube drainage, rapid initiation of anti-tuberculosis therapy, and consideration of surgical closure of BPF to prevent recurrence.

PAL—defined as an air leak persisting beyond 5–7 days—is a clear indication for surgical intervention. VATS with pleurodesis, bleb/cavity repair, or fistula closure is the current gold standard, reducing recurrence rates to < 10%, compared with ~50% with drainage alone and 10%–25% with chemical pleurodesis. ⁹

In this case, initial aspiration and oxygen therapy were selected because the pneumothorax was moderate and the patient’s respiratory symptoms were mild—an approach supported by BTS guidelines in selected young patients. ¹³ However, as the pneumothorax progressed and respiratory failure emerged, urgent chest tube drainage was required, consistent with recommendations and previous reports emphasizing timely intervention in TB-related SSP. ¹⁴

Despite chest tube placement, the patient developed PAL—common in tuberculous pneumothorax. Under normal circumstances, surgery would have been indicated. However, because of severe hepatitis B flare and high surgical risk, a conservative approach with individualized anti-TB therapy, liver-supportive treatment, oxygen supplementation, and later chemical pleurodesis was chosen.

This case highlights that, although surgical management remains the preferred strategy for TB-associated SSP with PAL, carefully selected patients with major contraindications may still achieve successful outcomes with optimized medical therapy.

The key distinguishing feature of this case is the exceptionally high surgical risk, driven by the patient’s severely compromised general condition, acute hepatitis B–related liver failure, and extensive bilateral pulmonary destruction. These factors together created a strong contraindication to thoracic surgery, which requires endotracheal anesthesia and carries significant risks of coagulopathy and mortality in the context of acute liver dysfunction. ⁸ In addition, the patient’s widespread consolidation, fibrosis, cavitation, and near-complete destruction of the right lung posed major operative challenges—including difficulty identifying the precise source of the air leak, determining the appropriate extent of surgical intervention, and assessing the functional reserve of the remaining lung tissue.

Another important factor in this case was the patient’s cachectic state at presentation. Marked weight loss, poor nutritional reserve, and systemic debilitation likely reflected prolonged inflammatory burden from extensive tuberculosis and may also have impaired tissue repair and delayed closure of the BPF, thereby contributing to the prolonged air leak. Cachexia may further increase vulnerability to treatment-related complications and reduce tolerance for invasive procedures. In this context, nutritional optimization was not merely supportive care but an important component of the overall management strategy. The coexistence of cachexia and prolonged air leak further complicated treatment decisions, as both factors reduced the likelihood of rapid spontaneous recovery while simultaneously increasing the risks associated with surgery. This may partly explain why clinical improvement required a prolonged course of individualized medical management before full radiologic resolution was achieved.

The treatment team, therefore, had to balance the surgical “gold standard” against the need for individualized, conservative management. Similar dilemmas have been described in the literature, in which severe comorbidities render surgery unsafe and require tailored treatment strategies. Nava and Walker ⁹ likewise emphasized that PAL management must be individualized when standard recommendations cannot be followed.

Betadine pleurodesis was performed as a non-surgical attempt to close the fistula. Although the patient’s respiratory function improved and he was able to maintain SpO₂ around 97% on room air, radiologic expansion of the right lung remained incomplete, likely because of a PAL preventing adequate pleural apposition. At this stage, another critical decision was made: early removal of the drainage tube to reduce the risk of pleural infection. Prolonged drainage in the setting of BPF increases susceptibility to secondary bacterial empyema—a serious and potentially fatal complication. Therefore, once the patient was clinically stable, the tube was removed despite persistent moderate pneumothorax, consistent with a “maximally conservative, minimally invasive” strategy appropriate for high-risk patients.

Anti-tuberculosis treatment was individualized according to the patient’s clinical response and liver function. First, in the setting of acute liver injury due to an exacerbation of chronic hepatitis B, an initial hepatosparing regimen consisting of imipenem/cilastatin, levofloxacin, ethambutol, and linezolid was selected to minimize hepatotoxicity while maintaining anti-tuberculosis efficacy. Second, once liver function had fully recovered, the treatment was adjusted back to the standard first-line RHZE regimen in accordance with guideline-recommended therapy. Third, following recurrence of liver injury after reintroduction of the standard regimen, the treatment was modified again to reduce hepatotoxic risk and to facilitate outpatient maintenance therapy, using rifampicin, ethambutol, levofloxacin, and linezolid. This stepwise approach highlights the need for flexibility and individualization in anti-tuberculosis management to balance therapeutic efficacy, drug tolerability, and the risk of hepatotoxicity (Table 1).

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Table 1.

Individualized adjustments to anti-tuberculosis regimens over time based on liver function and treatment response.

Treatment phase	Regimen	Clinical context	Rationale
Before admission	RHZE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol)	Outpatient treatment; bilateral pulmonary tuberculosis; Acid-Fast Bacilli (AFB)-positive sputum smear	Standard first-line regimen initiated in accordance with the National Tuberculosis Control Program.
At admission	Imipenem/cilastatin, levofloxacin, ethambutol, linezolid	Acute hepatic dysfunction with high risk of drug-induced liver injury due to acute exacerbation of hepatitis B	A hepatosparing regimen was selected to avoid or delay the most hepatotoxic first-line agents while maintaining anti-tuberculosis activity until liver function improved.
Seven days after admission	RHZE	Improvement in liver function and clinical stabilization	Stepwise reintroduction of the standard first-line regimen to maximize bactericidal and sterilizing efficacy once liver function permitted, consistent with guideline-supported re-challenge after recovery.
Seventeen days after admission	Rifampicin, ethambutol, levofloxacin, linezolid	Recurrent liver dysfunction and intolerance following re-challenge with RHZE	Regimen modified to balance effective tuberculosis control with safety by reducing hepatotoxic exposure and tailoring treatment according to tolerance and ongoing liver function monitoring.
Maintenance phase (until treatment completion)	Rifampicin, ethambutol, levofloxacin, linezolid	Good drug tolerance and sustained clinical improvement	Regimen maintained as continuation therapy to ensure treatment completion while preserving efficacy and minimizing the risk of recurrent hepatotoxicity.

In addition to individualized anti-tuberculosis therapy, intensive liver-directed supportive care likely played an important role in the patient’s recovery. This approach included metabolic support with intravenous glucose administration, hepatoprotective treatment, measures to facilitate ammonia detoxification and prevent hepatic encephalopathy, continuation of antiviral therapy for hepatitis B, and close monitoring with treatment adjustment according to liver function. Together with oxygen supplementation and nutritional support, these measures helped stabilize the patient’s general condition, improve hepatic function, and allow continuation of prolonged anti-tuberculosis treatment despite significant hepatic impairment.

The major clinical challenge occurred when the patient was readmitted with a progressive right pneumothorax. Although current guidelines generally recommend surgical intervention in such cases to prevent acute respiratory failure, we opted to continue conservative management. This non-standard management approach was justified by the patient’s remarkable clinical stability despite severe radiological findings on chest X-ray and computed tomography. Although the pneumothorax demonstrated radiological progression, the patient showed no signs of acute respiratory failure. Moreover, the patient’s poor general condition and impaired hepatic function, accompanied by coagulation abnormalities, would have posed substantial perioperative risks had surgical intervention been pursued. Therefore, invasive procedures such as emergency surgery or pleural drainage were reserved for situations with clear clinical evidence of life-threatening acute respiratory compromise. This case underscores an important principle: in complex, high-risk situations, clinical physiology should guide decision making more than imaging severity when considering invasive interventions. ¹¹

The patient’s favorable outcome validates this approach. After 6 months of optimized anti-tuberculosis therapy and intensive nutritional support, the pneumothorax fully resolved and liver function normalized. This outcome demonstrates that conservative management can be successful in recurrent TB-related pneumothorax, particularly when surgery is contraindicated. It also highlights that in TB-related BPF, the key factor enabling spontaneous closure is effective microbiologic control of tuberculosis, allowing the necrotic parenchyma to heal. This mechanism differs from emphysema- or bullae-related pneumothorax, where structural defects are irreversible and typically require surgical correction.^15,16

Another essential component of conservative therapy was the use of supplemental oxygen. The physiologic basis of oxygen therapy is the “nitrogen washout” effect, which lowers alveolar nitrogen content and increases the partial pressure gradient between the pleural space and the pulmonary capillaries. This accelerates diffusion of nitrogen from the pleural cavity into the bloodstream, thereby promoting faster absorption of the pneumothorax. Studies have shown that supplemental oxygen can enhance pleural gas absorption rates by two- to four-fold compared with room air.^17,18

Conclusion

In patients with pulmonary tuberculosis complicated by recurrent or persistent secondary spontaneous pneumothorax, conservative management may still be successful when clinical symptoms remain stable and acute respiratory failure is absent, even in the presence of severe pneumothorax on imaging. In such cases, an aggressive, comprehensive, and closely monitored conservative approach represents a valid therapeutic option for selected high-risk patients. Nevertheless, conservative management should be individualized and reserved for patients with clear contraindications to surgery, rather than being applied universally to all cases of pulmonary tuberculosis with persistent air leaks. When acute lung compression leads to respiratory dysfunction or respiratory failure, pleural drainage should be the preferred intervention.

Ultimately, optimization of anti-tuberculosis therapy remains the cornerstone of management, as effective control of active tuberculosis is essential for healing parenchymal destruction and promoting closure of the air leak. Adjunctive measures—including pleural air drainage, supplemental oxygen, and nutritional support—play important supportive roles in stabilizing respiratory function and facilitating overall clinical recovery.

Supplemental Material