Short summary

Single-center retrospective cohort study evaluating the incidence of chronic pulmonary aspergillosis infections in a suspected high-risk population of danish patients suspected of pulmonary malignancy from 2016 to 2019. Patient examination process and diagnosis is audited according to predetermined criteria and up to date international guidelines.

Study aims to assess:

-          CPA incidence among patients referred for chest-malignancy examination

-          Characteristics and subtype of identified CPA patients

-          A diagnostic algorithm to ensure identification of CPA with a high sensitivity

Rationale

 Chronic pulmonary aspergillosis (CPA) is a life-threatening and neglected pulmonary fungal infection. It is estimated that more than 3 million people are suffering of CPA worldwide [1]. National and international studies on CPA incidence are still relatively scarce and in a clinical context CPA is by many considered as being a rare condition. But some of the currently published studies indicate that the incidence may be relatively high in selected populations [2]. The estimated 5-year mortality rate of CPA is estimated to be 40-80% depending on comorbidities and CPA subtype [3, 4]. Tools for early diagnosis and antifungal treatment are therefore crucial aspects in order to improve the individual patient's long-term survival.

Early diagnosis of CPA is clinically difficult since the symptoms (e.g. breathlessness, sputum production, hemoptysis, malaise, weight loss, low grade fever) and imaging (e.g. opacity, cavitation) is very similar to other common respiratory diseases (e.g. lung cancer, tuberculosis, chronic obstructive pulmonary disease, emphysema) [1, 2, 5]. Additionally, these conditions are known risk factors for developing CPA and the patient might therefore suffer from several severe respiratory diseases simultaneously [1, 4, 5].

In a Danish context, patients with the above-mentioned symptoms and imaging findings would often be referred for assessment of possible malignancy in the chest. This patient population could therefore potentially have a high incidence of CPA with the possibility of early diagnosis if the optimal diagnostics are chosen. No studies have however previously assessed the incidence of CPA or the optimal CPA diagnostic approach in such a patient population.

References

1. Denning DW, Cadranel J, Beigelman-Aubry C, Ader F, Chakrabarti A, Blot S, Ullmann AJ, Dimopoulos G, Lange C, European Society for Clinical M, Infectious D, European Respiratory S. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology 2016: 47(1): 45-68.

2. Page ID, Byanyima R, Hosmane S, Onyachi N, Opira C, Richardson M, Sawyer R, Sharman A, Denning DW. Chronic pulmonary aspergillosis commonly complicates treated pulmonary tuberculosis with residual cavitation. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology 2019: 53(3).

3. The Lancet Respiratory M. Chronic pulmonary aspergillosis: help is on the way. The Lancet Respiratory medicine 2016: 4(2): 83.

4. Lowes D, Al-Shair K, Newton PJ, Morris J, Harris C, Rautemaa-Richardson R, Denning DW. Predictors of mortality in chronic pulmonary aspergillosis. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology 2017: 49(2).

5. Bongomin F, Harris C, Hayes G, Kosmidis C, Denning DW. Twelve-month clinical outcomes of 206 patients with chronic pulmonary aspergillosis. PloS one 2018: 13(4): e0193732.

Description of the cohort

Any patient referred and accepted for examination according to the Lung Cancer package at the Center of Thoracic Oncology at the department of respiratory medicine (J), Odense University Hospital (OUH) between 2016 to 2019, using intention-to-treat analysis.

The candidate population has been collected by export of patients with the diagnosis code DZ031B and DZ031BR.

There is some limitation to the chronology of diagnosis code assignment, but we aim to include 1000 patients from "newest" to "oldest", meaning patients coded in 2019 first, then 2018 etc.

Exclusion criteria:

-          Prior examination in the lung cancer package

Data and biological material

- Baseline characteristics such as comorbidity, medication, selected exposures and lung-status

- Referral information and symptoms at time of referral

- Examination procedures and results, such as biochemistry, invasive procedures, pathology, microbiology and radiology

- Diagnosis and events until 31/12/2019

Collaborating researchers and departments

Department of Respiratory Medicine, Odense University Hospital

• Associate Professor Jesper Rømhild Davidsen, MD, PhD
• Clinical Professor Christian Borbjerg Laursen, MD, PhD