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

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.

Download Full-text

Risk factors for chronic pulmonary aspergillosis in a low prevalence country and their effect on survival

10.1183/13993003.congress-2015.pa2653 ◽

2015 ◽

Author(s):

Nils Hoyer ◽

Jørgen Vestbo

Keyword(s):

Risk Factors ◽

Pulmonary Aspergillosis ◽

Chronic Pulmonary Aspergillosis ◽

Low Prevalence

Download Full-text

The Efficacy and Safety of Surgical Treatment for Patients With Tuberculosis Destroyed Lung With or Without Chronic Pulmonary Aspergillosis

World Journal of Surgery ◽

10.1007/s00268-021-05969-w ◽

2021 ◽

Author(s):

Hongyun Ruan ◽

Changfan Gong ◽

Jinxiang Wang

Keyword(s):

Risk Factors ◽

Surgical Treatment ◽

Postoperative Complications ◽

Postoperative Mortality ◽

Efficacy And Safety ◽

Pulmonary Aspergillosis ◽

Preoperative Serum ◽

Chronic Pulmonary Aspergillosis ◽

Independent Risk Factors ◽

Destroyed Lung

Abstract Background To evaluate the efficacy and safety of surgical treatment of tuberculosis destroyed lung (TDL), and the influence of chronic pulmonary aspergillosis (CPA) on the outcomes of surgical treatment of TDL. Methods We performed a retrospective analysis of 113 patients with TDL who underwent surgical treatment from January 2005 to December 2019. Among them, 30 of these cases were complicated with CPA. The patients were divided into two groups: TDL group and TDL + CPA group. We analyzed the effectiveness and safety of surgical treatment of TDL, and further compared the effectiveness and safety of surgical treatment of TDL with or withoutthe presence of CPA. Results The TDL + CPA group had a significantly higher age (P=0.003), symptoms of hemoptysis (P=0.000), and a higher proportion of patients with preoperative serum albumin <30 g/L (P=0.014) as compared with TDL group. For all enrolled patients, the incidence of severe postoperative complications was 12.4% (14/113) and the postoperative mortality within 30 days after discharge was 4.4% (5/113). 86.7% (98/113) of the patients recovered and discharged, the incidence of severe postoperative complications in the TDA + CPA group was higher than that of TDL group (23.3% vs 8.4%, P = 0.034), although there was no difference in mortality between the two groups (P = 1.000). A binary logistic regression analysis showed that the independent risk factors for severe postoperative complications were male (OR 25.24, 95% CI 2.31–275.64; P = 0.008) and age ≥ 40 years (OR 10.34, 95% CI 1.56–68.65; P = 0.016). Conclusion Surgical treatment for patients with TDL is effective with an acceptable mortality rate whether or not the disease is complicated with CPA. The independent risk factors identified for severe postoperative complications in patients with TDL were male and ≥ 40 years old. It implies that when treating patients with TDA + CPA, particular attention should be paid to these patients who have these independent risk factors to avoid a poor outcome.

Download Full-text

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

Frontiers in Medicine ◽

10.3389/fmed.2021.777457 ◽

2022 ◽

Vol 8 ◽

Author(s):

Katarzyna Guziejko ◽

Katarzyna Klukowska ◽

Urszula Budzińska ◽

Robert Marek Mróz

Keyword(s):

Lung Cancer ◽

Fungal Infection ◽

Antifungal Therapy ◽

Rare Complication ◽

Locally Advanced ◽

Delayed Diagnosis ◽

Pulmonary Aspergillosis ◽

Radical Treatment ◽

Significant Clinical Improvement ◽

Chronic Pulmonary Aspergillosis

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.

Download Full-text

Risk factors for chronic pulmonary aspergillosis in post-TB patients

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.20.0735 ◽

2021 ◽

Vol 25 (4) ◽

pp. 324-326

Author(s):

R. Singla ◽

R. Singhal ◽

R. Rathore ◽

A. Gupta ◽

P. Sethi ◽

...

Keyword(s):

Risk Factors ◽

Pulmonary Aspergillosis ◽

Chronic Pulmonary Aspergillosis

Download Full-text

Risk factors and treatment outcomes in patients with chronic pulmonary aspergillosis

10.1183/13993003.congress-2016.pa2647 ◽

2016 ◽

Author(s):

Kshitij Agarwal ◽

Anuradha Chowdhary ◽

M. Rahman ◽

Anil Chaudhry ◽

S.N. Gaur

Keyword(s):

Risk Factors ◽

Treatment Outcomes ◽

Pulmonary Aspergillosis ◽

Chronic Pulmonary Aspergillosis

Download Full-text

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.

Download Full-text

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.

Download Full-text

Clinical manifestations, associated risk factors and treatment outcomes of Chronic Pulmonary Aspergillosis (CPA): Experiences from a tertiary care hospital in Lahore, Pakistan

PLoS ONE ◽

10.1371/journal.pone.0259766 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0259766

Author(s):

Waqas Akram ◽

Muhammad Bilal Ejaz ◽

Tauqeer Hussain Mallhi ◽

Syed Azhar bin Syed Sulaiman ◽

Amer Hayat Khan

Keyword(s):

Risk Factors ◽

Treatment Response ◽

Hematological Malignancies ◽

Clinical Manifestations ◽

Response Rates ◽

Pulmonary Aspergillosis ◽

Factors Associated ◽

Icu Admission ◽

Chronic Pulmonary Aspergillosis ◽

The Mean

Background Chronic pulmonary aspergillosis (CPA) has a wide spectrum of illnesses depending on the progression of the disease and comorbid conditions. However, there is an inadequacy of investigations regarding clinical, laboratory, risk factor and prognostic data on CPA. The current study is aimed to consider the clinical manifestations, risk factors and outcomes of CPA. Methodology Retrospective records of all patients with a confirmed diagnosis of CPA who sought treatment at Gulab Devi Chest Hospital Lahore, Pakistan from January 2017 to December 2019 were evaluated. Data regarding demographics, clinical manifestations, comorbidities, radiographic and microbiological findings, length of hospital stay (LOS) and intensive care unit (ICU) admission was collected and analyzed to identify the factors associated with mortality. The independent factors associated with mortality were also identified by appropriate analyses. Results A total of 218 CPA patients were included in this study. The mean age was 45.75 ± 6.26 years. Of these, 160 (73.4%) were male, and 65 (29.8%) had diabetes. The mean LOS was 18.5 ± 10.9 days. The most common type of CPA was simple aspergilloma (56%) followed by chronic cavitary pulmonary aspergillosis (CCPA) (31.2%). About one half of the patients had a history of pulmonary tuberculosis (TB) and treatment response rates were low in patients with active TB. The overall mortality rate was 27.1%. ICU admission was required for 78 (35.8%) patients. Diabetes mellitus (DM), hematological malignancies and chronic kidney disease (CKD) were the common underlying conditions predicting a poor outcome. Mean LOS, hematological malignancies, consolidation and ICU admission were identified as the independent factors leading to mortality. Conclusions CPA had a significant association with TB in the majority of cases. Treatment response rates in cases with active TB were comparatively low. Cases with high mean LOS, hematological malignancies, consolidation, ICU admission, CKD and DM experienced poor outcomes. High mean LOS, hematological malignancies, consolidation and ICU stay were identified as independent risk factors for mortality. Future large prospective studies, involving aspergillus specific immunoglobulin G (IgG) antibody testing, are required for a better understanding of CPA in Pakistan.

Download Full-text