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Serial imaging of COPD exacerbation on immunotherapy. Representative apical, mid and basilar lung fields are shown by timepoint in columns for Case 2. There was no evidence of pneumonitis or another pulmonary cause of this patient's breathing difficulties and a cardiac evaluation was negative.
Source publication
Background
Immune checkpoint inhibitor therapy is rapidly becoming front line adjuvant or primary therapy in a number of solid cancer types. Since many of these cancers are a result of tobacco smoking, a large number of these patients will have underlying comorbid conditions attributed to smoking such as Chronic Obstructive Pulmonary Disease (COPD)...
Context in source publication
Context 1
... of the next two months, she had progressive symptom deterioration and was placed on a slow prednisone taper for one month by our pulmonary team. She subsequently developed pneumonia and atrial fibrillation and was placed on hospice at month 12. Her CT scans prior to ICI initiation and at months 1, 4, and 7 demonstrated no evidence of pneumonitis (Fig. 2). A diagnosis of refractory COPD exacerbation from ICI therapy was invoked. She expired 15 months after ICI initiation from metastatic lung cancer and ...
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Citations
... ICI therapy has been linked to several complications that affect the lungs. These include sarcoid-like granulomatosis (34)(35)(36)(37), pleural effusion (38), exacerbation of obstructive lung disease (37,(39)(40)(41)(42)(43), and, most notably, CIP. Among these complications, CIP is the most widely recognized and is of serious concern due to its high morbidity and mortality rates (12,44). ...
Cancer remains a leading cause of mortality on a global scale. Lung cancer, specifically non-small cell lung cancer (NSCLC), is a prominent contributor to this burden. The management of NSCLC has advanced substantially in recent years, with immunotherapeutic agents, such as immune checkpoint inhibitors (ICIs), leading to improved patient outcomes. Although generally well tolerated, the administration of ICIs can result in unique side effects known as immune-related adverse events (irAEs). The occurrence of irAEs involving the lungs, specifically checkpoint inhibitor pneumonitis (CIP), can have a profound effect on both future therapy options and overall survival. Despite CIP being one of the more common serious irAEs, limited treatment options are currently available, in part due to a lack of understanding of the underlying mechanisms involved in its development. In this Review, we aim to provide an overview of the epidemiology and clinical characteristics of CIP, followed by an examination of the emerging literature on the pathobiology of this condition.
... COPD was also associated with longer progression-free intervals when compared with those without COPD. [15] However, there have been case reports of both severe bronchiolitis [16][17][18] and COPD exacerbations [19] in association with ICI treatment. The diagnosis of airway exacerbations is made difficult by the commonality of certain symptoms, like dyspnea and cough, with the primary cancer. ...
Pulmonary toxicity from immune checkpoint inhibitor therapy is typically a severe and potentially fatal complication, but these observations are driven by the most common toxicity, pneumonitis. Rarer pulmonary immune related adverse events, like airway disease and sarcoidosis, may have a more benign course. In this case report, we present a patient in whom therapy with the PD-1 inhibitor pembrolizumab resulted in severe eosinophilic asthma and sarcoidosis. This is the first case showing that anti–IL-5 inhibition may be safe in patients who develop eosinophilic asthma after ICI therapy. We further show that sarcoidosis does not necessarily require treatment cessation. This case highlights relevant nuances when clinicians face pulmonary toxicities other than pneumonitis.
... Since it is biologically plausible for immunotherapy to stimulate lymphocytes against healthy lung cancer cells, increasing lung tissue damage and COPD symptoms. Nair et al. reported a series of patients with prolonged and severe COPD exacerbations upon initiating immune checkpoint inhibitor therapy, indicating ICIs may aggravate CODP and irAE [27]. However, given the stringent eligibility criteria applied in clinical trials, healthier patients tend to be enrolled, and thus the real-world frequency of these events in the overall population is unknown. ...
Objectives
Chronic obstructive pulmonary disease (COPD) is the most common co-morbidity associated with non-small cell lung cancer (NSCLC) patients. Immune checkpoint inhibitors related pneumonitis (CIP) is a common immune-related adverse event that can be life-threatening. The study aims to evaluate the association of COPD with the incidence and outcome of CIP in NSCLC patients receiving immune checkpoint inhibitors (ICIs).
Materials and methods
We retrospectively collected data from 122 patients diagnosed with NSCLC and treated with ICIs in our department. Baseline pulmonary function was performed in the whole cohort. The incidence, risk factors, treatment and outcome of CIP patients were evaluated. Furthermore, the efficacy of ICIs in patients with COPD was analyzed.
Results
Nineteen patients (15.5%, 19/122) developed CIP during ICIs treatment, most patients with CIP were grade 1–2, and the incidence of CIP was comparable in patients with COPD and those without COPD (18.0% vs. 13.1%, P = 0.618). In addition, an increasing trend in the incidence of CIP among patients with pulmonary fibrosis on baseline chest CT scans (27.3% vs. 13.0%, P = 0.093). There is a longer progression-free survival in COPD patients than the non-COPD patients.
Conclusion
Coexisting COPD did not predict the higher risk of CIP in NSCLC treated with ICIs therapy. Nevertheless, pre-existing pulmonary fibrosis on CT scan may increase the risk of CIP, close monitoring is advised in these patients during ICIs.
Immune checkpoint inhibitors (ICI) are widely used for the treatment of various malignant neoplasms. Interstitial lung disease is a well-known immune-related adverse event, however, ICI-induced airway disease remains under-recognized. Herein, we report two similar cases of pembrolizumab-induced tracheobronchitis presenting as persistent chronic cough and dyspnea. Blood tests revealed elevated C-reactive protein levels without eosinophilia. Spirometry demonstrated mild airflow obstruction. Computed tomography revealed diffuse thickening of the tracheobronchial walls and bronchiectasis predominantly in the lower lobes. Bronchoscopy revealed edematous and erythematous tracheobronchial mucosa, and bronchial biopsy tissue exhibited marked inflammation with predominant infiltration of CD8+ lymphocytes. Subsequently, pembrolizumab-induced tracheobronchitis was diagnosed in both cases. Cessation of pembrolizumab and initiation of erythromycin, inhaled corticosteroids, and long-acting beta-agonists gradually improved the symptoms, airflow obstruction, and radiographic findings. These were completely resolved in one case. The other case initially showed a poor response to systemic corticosteroids combined with the aforementioned drugs, but improved gradually and almost completely. These cases exemplify ICI-induced airway disease that is, an under-recognized manifestation of immune-related adverse events. In addition, we have systematically searched the PubMed database for articles on ICI-induced airway disease, categorized the retrieved articles as eosinophilic and non-eosinophilic airway diseases, and reviewed the differences in treatment and prognoses between these two categories.
Many studies have proved that the pathogenesis of the chronic obstructive pulmonary disease (COPD) and lung cancer is related, and may cause and affect each other to a certain extent. In fact, the change of chronic airway obstruction will continue to have an impact on the screening, treatment, and prognosis of lung cancer.In this comprehensive review, we outlined the links and heterogeneity between COPD and lung cancer and finds that factors such as gene expression and genetic susceptibility, epigenetics, smoking, epithelial mesenchymal transformation (EMT), chronic inflammation, and oxidative stress injury may all play a role in the process. Although the relationship between these two diseases have been largely determined, the methods to prevent lung cancer in COPD patients are still limited. Early diagnosis is still the key to a better prognosis. Thus, it is necessary to establish more intuitive screening evaluation criteria and find suitable biomarkers for lung cancer screening in high-risk populations with COPD. Some studies have indicated that COPD may change the efficacy of anti-tumor therapy by affecting the response of lung cancer patients to immune checkpoint inhibitors (ICIs). And for lung cancer patients with COPD, the standardized management of COPD can improve the prognosis. The treatment of lung cancer patients with COPD is an individualized, comprehensive, and precise process. The development of new targets and new strategies of molecular targeted therapy may be the breakthrough for disease treatment in the future.
