Case Report: Chronic Pulmonary Aspergillosis—An Unusual Long-Term Complication of Lung Cancer Treatment

Background: Chronic pulmonary aspergillosis (CPA) is a rare complication of radiochemotherapy for lung cancer. It may develop months or years after radical treatment. The diagnosis of CPA is challenging and complex. Not only fungal infection but also cancer relapse always have to be taken under consideration. Antifungal therapy is the base treatment, especially in the case when a surgical procedure is not possible. Standard treatment for at least 6 months is recommended but the optimal duration of the antifungal therapy is unknown. We present the clinical case of CPA, in which we had to perform multidirectional diagnostic tests to confirm the diagnosis and modified treatment due to the recurrence of the disease.Case Presentation: We report a patient who developed CPA three and a half years after concurrent radiochemotherapy for locally advanced non-small-cell lung cancer. Non-specific symptoms were the cause of delayed diagnosis of fungal infection. Samples collected during bronchoscopy allowed to exclude the recurrence of lung cancer and establish the diagnosis of CPA. The patient was treated with itraconazole for 6 months. A few months later, controlled chest CT scans revealed the progression of CPA. Initially, retreatment with itraconazole was implemented. Due to the progression of fungal infection, voriconazole was used in the second line of treatment. Unfortunately, this therapy was complicated by the side effects and deterioration of the patient's condition. The reintroduction of itraconazole resulted in clinical and radiological improvement. Treatment is scheduled for at least 12 months.Conclusion: Chronic pulmonary aspergillosis (CPA) was the cause of clinical deterioration and radiological progression in a patient after the radical treatment of lung cancer. In the described case, the diagnosis of CPA was delayed because of the suspicion of the recurrence of lung cancer. As the surgery was not possible, antifungal therapy with itraconazole was implemented and the proper dosage and duration led to significant clinical improvement.

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Incidence and Risk Factors of Chronic Pulmonary Aspergillosis Development during Long-Term Follow-Up after Lung Cancer Surgery

Journal of Fungi ◽

10.3390/jof6040271 ◽

2020 ◽

Vol 6 (4) ◽

pp. 271

Author(s):

Sun Shin ◽

Bo-Guen Kim ◽

Jiyeon Kang ◽

Sang-Won Um ◽

Hojoong Kim ◽

...

Keyword(s):

Lung Cancer ◽

Cumulative Incidence ◽

Lung Cancer Surgery ◽

Cancer Surgery ◽

Pulmonary Aspergillosis ◽

Factors Associated ◽

Long Term Follow Up ◽

Chronic Pulmonary Aspergillosis

Lung resection surgery for non-small-cell lung cancer (NSCLC) is reportedly a risk factor for developing chronic pulmonary aspergillosis (CPA). However, limited data are available regarding the development of CPA during long-term follow-up after lung cancer surgery. This study aimed to investigate the cumulative incidence and clinical factors associated with CPA development after lung cancer surgery. We retrospectively analyzed 3423 patients with NSCLC who (1) underwent surgical resection and (2) did not have CPA at the time of surgery between January 2010 and December 2013. The diagnosis of CPA was based on clinical symptoms, serological or microbiological evidences, compatible radiological findings, and exclusion of alternative diagnoses. The cumulative incidence of CPA and overall survival (OS) were estimated using the Kaplan–Meier method, and a multivariable Cox proportional hazard analysis was performed to identify factors associated with CPA development. Patients were followed-up for a median of 5.83 years with a 72.3% 5-year OS rate. Fifty-six patients developed CPA at a median of 2.68 years after surgery, with cumulative incidences of 0.4%, 1.1%, 1.6%, and 3.5% at 1, 3, 5, and 10 years, respectively. Lower body mass index (BMI), smoking, underlying interstitial lung disease, thoracotomy, development of postoperative pulmonary complications 30 days after surgery, and treatment with both chemotherapy and radiotherapy were independently associated with CPA development. The cumulative incidence of CPA after surgery was 3.5% at 10 years and showed a steadily increasing trend during long-term follow-up. Therefore, increased awareness regarding CPA development is needed especially in patients with risk factors.

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Pulmonary aspergillosis as a late complication after surgery for locally advanced non-small cell lung cancer treated with induction chemoradiotherapy

Surgery Today ◽

10.1007/s00595-020-01960-5 ◽

2020 ◽

Vol 50 (8) ◽

pp. 863-871

Author(s):

Seiichiro Sugimoto ◽

Junichi Soh ◽

Ken Suzawa ◽

Kentaroh Miyoshi ◽

Shinji Otani ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Late Complication ◽

Locally Advanced ◽

Small Cell ◽

Small Cell Lung ◽

Pulmonary Aspergillosis ◽

Induction Chemoradiotherapy

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Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management

European Respiratory Journal ◽

10.1183/13993003.00583-2015 ◽

2015 ◽

Vol 47 (1) ◽

pp. 45-68 ◽

Cited By ~ 268

Author(s):

David W. Denning ◽

Jacques Cadranel ◽

Catherine Beigelman-Aubry ◽

Florence Ader ◽

Arunaloke Chakrabarti ◽

...

Keyword(s):

Antifungal Therapy ◽

Clinical Guidelines ◽

Bronchial Artery ◽

Invasive Pulmonary Aspergillosis ◽

Immunological Response ◽

Surgical Excision ◽

Immunocompromised Patients ◽

Pulmonary Aspergillosis ◽

Thoracic Imaging ◽

Chronic Pulmonary Aspergillosis

Chronic pulmonary aspergillosis (CPA) is an uncommon and problematic pulmonary disease, complicating many other respiratory disorders, thought to affect ∼240 000 people in Europe. The most common form of CPA is chronic cavitary pulmonary aspergillosis (CCPA), which untreated may progress to chronic fibrosing pulmonary aspergillosis. Less common manifestations include:Aspergillusnodule and single aspergilloma. All these entities are found in non-immunocompromised patients with prior or current lung disease. Subacute invasive pulmonary aspergillosis (formerly called chronic necrotising pulmonary aspergillosis) is a more rapidly progressive infection (<3 months) usually found in moderately immunocompromised patients, which should be managed as invasive aspergillosis. Few clinical guidelines have been previously proposed for either diagnosis or management of CPA. A group of experts convened to develop clinical, radiological and microbiological guidelines. The diagnosis of CPA requires a combination of characteristics: one or more cavities with or without a fungal ball present or nodules on thoracic imaging, direct evidence ofAspergillusinfection (microscopy or culture from biopsy) or an immunological response toAspergillusspp. and exclusion of alternative diagnoses, all present for at least 3 months.Aspergillusantibody (precipitins) is elevated in over 90% of patients. Surgical excision of simple aspergilloma is recommended, if technically possible, and preferablyviavideo-assisted thoracic surgery technique. Long-term oral antifungal therapy is recommended for CCPA to improve overall health status and respiratory symptoms, arrest haemoptysis and prevent progression. Careful monitoring of azole serum concentrations, drug interactions and possible toxicities is recommended. Haemoptysis may be controlled with tranexamic acid and bronchial artery embolisation, rarely surgical resection, and may be a sign of therapeutic failure and/or antifungal resistance. Patients with singleAspergillusnodules only need antifungal therapy if not fully resected, but if multiple they may benefit from antifungal treatment, and require careful follow-up.

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Aspergillus Sternomyelitis Developed from Chronic Pulmonary Aspergillosis as a Late Complication to Lobectomy for Lung Cancer

Internal Medicine ◽

10.2169/internalmedicine.0334-17 ◽

2018 ◽

Vol 57 (20) ◽

pp. 2991-2994

Author(s):

Yuji Uehara ◽

Hajime Kasai ◽

Takahiro Nakajima ◽

Nobuhiro Tanabe ◽

Koichiro Tatsumi ◽

...

Keyword(s):

Lung Cancer ◽

Late Complication ◽

Pulmonary Aspergillosis ◽

Chronic Pulmonary Aspergillosis

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High detection rate of azole-resistant Aspergillus fumigatus after treatment with azole antifungal drugs among patients with chronic pulmonary aspergillosis in a single hospital setting with low azole resistance

Medical Mycology ◽

10.1093/mmy/myaa052 ◽

2020 ◽

Cited By ~ 4

Author(s):

Keita Takeda ◽

Junko Suzuki ◽

Akira Watanabe ◽

Teppei Arai ◽

Tomohiro Koiwa ◽

...

Keyword(s):

Aspergillus Fumigatus ◽

Antifungal Therapy ◽

Detection Rate ◽

Hospital Setting ◽

Antifungal Drugs ◽

High Rate ◽

Therapy Failure ◽

National Hospital ◽

Pulmonary Aspergillosis ◽

Chronic Pulmonary Aspergillosis

Abstract The prevalence of azole-resistant Aspergillus fumigatus (ARAF) among chronic pulmonary aspergillosis (CPA) patients treated with azoles in Japan is unknown. The aim of this study was to determine the detection rate of ARAF in isolates from CPA patients who were treated with azoles for varying durations. The potential mechanism of acquiring resistance was examined by sequencing cyp51A and hmg1, two genes associated with ARAF. A. fumigatus isolates (n = 120) were collected from CPA patients (n = 104) between February 2012 and February 2019, at National Hospital Organization Tokyo National Hospital. The isolates were tested for susceptibility to the azole drugs itraconazole (ITCZ) and voriconazole (VRCZ). The detection rate of ARAF among all isolates was 8.3% (n = 10). Of the 10 resistant isolates, eight were ITCZ-resistant and five were VRCZ-resistant. Among 47 isolates obtained from 36 CPA patients who were treated with ITCZ (for an average of 256 days) and/or VRCZ (for an average of 29 days), the resistance rates were 17.0% and 10.6%, respectively. In addition, 46.2% of 13 isolates obtained from CPA patients with ongoing azole treatment at the time of antifungal therapy failure were resistant to azoles. Among the 10 ARAF isolates, a point mutation was detected in cyp51A in seven isolates and in hmg1 in two isolates. ARAF was detected at a high rate in CPA patients, particularly in those with ongoing long-term azole treatment, at the time of azole antifungal therapy failure.

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Risk factors for relapse of chronic pulmonary aspergillosis after discontinuation of antifungal therapy

Clinical Infection in Practice ◽

10.1016/j.clinpr.2020.100015 ◽

2020 ◽

Vol 5 ◽

pp. 100015 ◽

Cited By ~ 3

Author(s):

Felix Bongomin ◽

Akaninyene Otu ◽

Chris Harris ◽

Philip Foden ◽

Chris Kosmidis ◽

...

Keyword(s):

Risk Factors ◽

Antifungal Therapy ◽

Pulmonary Aspergillosis ◽

Chronic Pulmonary Aspergillosis

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Utility of St. George’s respiratory questionnaire in predicting clinical recurrence in chronic pulmonary aspergillosis

Therapeutic Advances in Infectious Disease ◽

10.1177/20499361211034643 ◽

2021 ◽

Vol 8 ◽

pp. 204993612110346

Author(s):

Felix Bongomin ◽

Akaninyene Otu

Keyword(s):

Quality Of Life ◽

Antifungal Therapy ◽

Disease Recurrence ◽

Self Assessment ◽

Pulmonary Aspergillosis ◽

Clinical Recurrence ◽

St George's Respiratory Questionnaire ◽

Chronic Pulmonary Aspergillosis ◽

The Impact

Background and Aims: Patients with chronic pulmonary aspergillosis (CPA) who discontinue antifungal therapy commonly exhibit disease recurrence. We aimed to evaluate the utility of the St. George’s respiratory questionnaire (SGRQ) in predicting the likelihood of clinical recurrence of CPA in patients who come off antifungal therapy. Methods: This audit included CPA patients for whom antifungal therapy was discontinued for at least 1 month. Comparisons were made between the quality of life scores at the time of discontinuation of treatment and at the time of diagnosis of clinical recurrence. The change in patients’ self-assessment scores was also compared. Results: There were 33 cases and 44 controls. Of the 33 cases, 22 (67%) were males with a mean age of 62 ± 13 years. The median for the symptom component of quality of life (QoL) changed from 78.4 at the time of discontinuation of therapy to 83.1 units at the time of diagnosis of clinical failure ( p = 0.043), whereas that of the impact and activity components changed from 62.7 to 59.1 units ( p = 0.387) and 85.0 to 85.9 units ( p = 0.153), respectively. At 12 months, the symptoms domain of SGRQ was able to discriminate between cases of clinical recurrence and controls [area under the curve (AUC) 0.7, 95% confidence interval (CI): 0.6–0.8, p = 0.009]. The proportion of patients in very poor health status increased from 3/11 (9.1%) to 11/33 (33.3%) ( p = 0.046). Conclusion: A deteriorating symptoms component of the SGRQ and a worsening of patients’ self-assessment are associated with clinical recurrence. Failure to improve by >8 units in the symptoms domain appear to be a marker of disease recurrence. We propose that the clinical approach to diagnose recurrent CPA would be a combination of clinical history, SGRQ scoring, chest imaging and a workup to exclude other causes of the patients’ symptoms.

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