Early-Onset COPD and Lung Cancer: Case Studies Highlighting Diagnostic Challenges in Younger Patients

Abstract

Case series

Patients: Male, 46-year-old • Female, 53-year-old • Female, 50-year-old

Final Diagnosis: Lung cancer

Symptoms: Cough

Clinical Procedure: —

Specialty: Oncology

Objective:

Rare coexistence of disease or pathology

Background:

The coexistence of lung cancer with COPD has received increasing attention in recent years. These 2 entities are attributed to older age, with a mean age of around 70 years old. Here, we present 3 fatal cases of lung cancer and COPD in uncommonly young patients (45–55 years old).

Case Reports

The first patient, 46-year-old man, reported progressive tiredness, and recurrent sub-febrile states, without recovery despite empiric treatment with 3 antibiotics. He was diagnosed with SCC and referred for chemoradiotherapy, but he died within 6 months. The second patient was 53-year-old women with hemoptysis, tiredness, loss of weight, spine pain, and cough, who was first diagnosed with pneumonia. Her first bronchoscopy was not diagnostic. A second bronchoscopy performed 2 weeks later was successful and she was diagnosed with large-cell carcinoma. She was referred for chemoradiotherapy, but died within 1 month. The third patient was 50-year-old women with chest pain radiating to her left shoulder and hoarseness. She was diagnosed with advanced SCLC, and was referred immediately for chemotherapy with immunotherapy, but did not respond well to treatment and died a few months later.

Conclusions:

Age seems to be one of the factors that can delay cancer diagnosis. To the best of our knowledge, the literature contains no reports about young patients with coexistence of lung cancer and COPD. We emphasize the importance of these diseases in differential diagnosis in younger patients when reported with systemic symptoms.

Introduction

Lung cancer is the second most commonly diagnosed cancer. Its prognosis is very poor, and in most countries only 10–20% of patients survive 5 years after diagnosis [1]. Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, with over 3.3 million deaths yearly [2]. Both of these diseases are associated with older age, with mean age around 70 years [3]. Only about 10% of patients diagnosed with either of these diseases are under 55 years old [4,5]. Age under 55 years is even less frequent among patients with coexistence of lung cancer and COPD, at less than 2% [6], although every year around 15 000 young patients are diagnosed with these 2 diseases worldwide [2]. Smoking remains the main risk factor for developing both diseases. Cigarette smoking increases lung cancer risk by 10-fold to 30-fold, with a proportional relationship with the number of cigarettes and the number of years smoked. There is similar relationship between smoking and COPD [6].

Case Reports

Case 1

Patient 1 was a 46-year-oldman with a history of 50 pack-years of tobacco smoking, without diagnosed diseases, who was admitted to the Department of Pulmonary Diseases. He reported progressive tiredness in the last 5 months that at first did not bother him, and in the last 1.5 months had recurrent sub-febrile states, productive cough, and occasional dyspnea. Symptoms did not resolve despite empiric treatment with 3 antibiotic therapies. He was not taking any long-term medications and had not been diagnosed with any disease. He lived a city with over 500 000 inhabitants, in a flat on the third floor with his wife and son, and worked in an office. His parents and wife were also smokers. During admission he was in fairly good general condition and his vital signs were within normal limits. Physical examination revealed muted vesicular breath sounds at the bottom of the left lung. Laboratory blood tests revealed a high white blood cell count and elevated C-reactive protein: WBC 16.9×10⁹/l, NEU 13.8×10⁹/l, CRP 91.6 mg/l. Chest X-ray revealed a large mass in the left lung, and extending to the mediastinum. A CT scan showed a nodular lesion in the left lung in. An abdominal ultrasound showed no abnormal results. Lung spirometry revealed moderate irreversible airflow obstruction: FEV1=2.30l, 61% of predicted value, FVC=3.71l, 78% of predicted value, FEV1/FVC=62.11%, and after 400 mcg of salbutamol FEV1=2.40l, 64% of predicted value, FVC=3.73l, 79% of predicted value, FEV1/FVC=64.21%. After exclusion of other causes of irreversible obstruction, grade B (GOLD) COPD was diagnosed. Treatment with tiotropium, long-acting muscarinic antagonist (LAMA), and salbutamol in case of dyspnea was started. Because of the findings in the CT, bronchoscopy was performed, which showed an exophytic tumor in the ostium of the left upper-lobe bronchus, and a bronchial biopsy was taken from this tumor. Additionally, transbronchial biopsy of a lymph node from group 7 supplied material for histopathologic examination. Finally, squamous cell carcinoma was confirmed. His lung cancer was staged as IIIB (T3N2M0). After an oncology team discussion, he was referred for chemoradiotherapy. He died 6 months after his diagnosis of lung cancer due to pneumonia complicated by COPD not responding to targeted antibiotic treatment (Table 1).

Table 1.

Timeline for patient’s diagnosis, treatment, and progression.

Timeline (46-year-old patient)		−5 months	−1.5 months	0	0–6 months	+6 months
Sequence of events		Progressive tiredness, not bothering patient at first	Recurrent subfebrile states	Hospitalization – lung cancer diagnosis, COPD diagnosis	Chemoradiotherapy	Death
Diagnostic Pathway				Chest X-ray lungs CT scan, bronchoscopy, spirometry,
Timeline (53-year-old patient)	−5 months	−2.5 months	−2 weeks	0	0–17 days	+17 days
Sequence of events	COPD Diagnosis	Hemoptysis, cough, tiredness, dyspnea, loss of weight, pain of thoracic spine	Hospitalization and treatment of pneumonia	Hospitalization Lung cancer diagnosis	Referral for chemoradiotherapy	Death
Diagnostic Pathway	Spirometry		Bronchoscopy	Chest X-ray lungs CT scan, bronchoscopy, histopathology
Timeline (50 years old patient)		−2 weeks	0	0–5 months	+5 months	+8 months
Sequence of events		Chest pain radiating to her left shoulder for couple days and hoarseness	Hospitalization Lung cancer and COPD diagnosis	Chemotherapy with immunotherapy carboplatin, etoposide, atezolizumab	Hospitalization: drug-induced (atezolizumab) autoimmunologic encephalitis	Death
Diagnostic Pathway			Chest X-ray lungs CT scan, bronchoscopy, spirometry		MRI and cerebrospinal fluid analysis

Case 2

Patient 2 was a 53-year-old woman with a history of 30 pack-years of tobacco smoking, treated COPD in grade B (GOLD), hypertension, and history of surgery for a hip fracture 5 years ago. She was admitted to the Department of Pulmonary Diseases for diagnostic bronchoscopy. She reported having hemoptysis, tiredness, exertional dyspnea, unintentional loss of weight, cervical and thoracic spine pain, and a cough. Lung spirometry performed 5 months before revealed moderate irreversible airflow obstruction: FEV1=0.91l, 41% of predicted value, FVC=1.631l, 58% of predicted value, FEV1/FVC=55.96%, and after 400 mcg of salbutamol FEV1=1.14l, 66% of predicted value, FVC=1.87l, 79% of predicted value, FEV1/FVC=60.72%. After exclusion of other causes of irreversible obstruction and with symptoms as productive cough, COPD was diagnosed in a grade B (GOLD). During her most recent hospitalization, FEV1 was 0.87l (39% of predicted value). She lived in a city with more than 100 000 inhabitants in a semi-detached house with husband, and worked as a shop assistant. Her father and husband were smokers, but her mother was not. She was hospitalized 2 weeks earlier in another department of pulmonary diseases with a diagnosis of pneumonia. The bronchoscopy performed during her previous hospitalization did not reveal pathologic changes, despite a large amount of suppurative secretion. The following lesions were described in her chest CT: the tumor was 68×87×82 mm in the hilum and segments 3, 5, and lower lobe of the right lung. The tumor surrounded the right main bronchus, and main bronchi of all lobes without the obstruction. The tumor pressed the superior vena cava in the proximal part measuring 4×14 mm and the right main pulmonary vein in the whole course. During admission, she was in fairly good general condition, with vital parameters within normal limits and 98% oxygen saturation. Physical examination revealed muted vesicular breath sounds at the middle and inferior lobe of the right lung. Laboratory blood tests revealed increased count of white blood cells and elevated level of C-reactive protein: WBC 33.55×10⁹/l, NEU 25.52×10⁹/l, LIMF 4.1×10⁹/l, CRP 106.9 mg/l. There were distension of the jugular veins and widened superficial vein on the upper-front chest, but peripheral lymph nodes were not enlarged. A second bronchoscopy showed widened main carina, edematous and hyperemic mucosa of bronchi to the upper- and middle-right lobes, and enlarged subcarinal lymph nodes (Figure 1). An aspiration biopsy was performed from subcarinal lymph nodes and supplied material for histopathologic examination, in which large-cell carcinoma was confirmed. Her lung cancer was staged as IIIB (T4N2M0). After oncology team discussion, the patient was referred for chemoradiotherapy, but she died 17 days after diagnosis of lung cancer during treatment of recurrent pneumonia complicated by COPD, not responding to targeted antibiotic treatment (Table 1).

Figure 1.

Bronchoscopy. Widened main carina (1), edematous and hyperemic mucosa of bronchi (2) to the upper and middle right lobes, and enlarged subcarinal lymph nodes.

Case 3

Patient 3 was a 50-year-old woman with a history of 35 pack-years of tobacco smoking and hypertension, who was admitted to the Department of Pulmonary Diseases. She reported chest pain radiating to her left shoulder for a few days and hoarseness. She lived alone in a detached house in a rural area and worked as an office worker. Her parents were smokers. During admission, she was in a fairly good general condition, and her vital signs were within normal limits except for blood pressure at 150/70 mmHG. Physical examination did not reveal abnormalities except for a scar after a cholecystectomy performed years ago. Laboratory blood tests revealed increased count of white blood cells and elevated level of C-reactive protein: WBC 11.02×10⁹/l, NEU 7.11×10⁹/l, CRP 18.3 mg/l. Myocardial infarction was excluded. A large mass in the middle region of the left lung interflowing with enlarged left hilum was described in the chest X-ray (Figure 2), which was specified as a spiculated 44×50×67 mm tumor in the left lung hilum on CT scan (Figure 3). The tumor touched the pulmonary trunk and the left pulmonary artery, and narrowed branches of the left pulmonary artery to segments 1+2 and 3. There were visible condensations in the lung’s parenchyma around the tumor in all segments of the upper-left lobe. Pathologically enlarged mediastinal, subclavicular left and cervical lymph nodes, and left hilum were detected. There was fluid in the left pleura but no signs of other metastases in the chest CT. Lung spirometry revealed irreversible severe airflow obstruction: Fev1=1.12l, 47% of predicted value, FVC=1.96l, 65% of predicted value, and FEV1/FVC=57.32%. After receiving 400 mcg of salbutamol, FEV1 was 1.43, 60% of predicted value, and FVC was 2.24l, 74% of predicted value. Her FEV1/FVC was 63.97%. A bronchodilator test was positive. After exclusion of other causes of irreversible obstruction, COPD was diagnosed in grade B (GOLD). Treatment with long-acting beta-agonists (LABA) was started. Bronchoscopy revealed an exophytic tumor closing bronchus LB3 (Figure 4). Endobronchial biopsy of the tumor supplied material for histopathologic examination, and transbronchial needle aspiration (TBNA) for lymph nodes groups 4b and 7 and small-cell lung carcinoma was confirmed in all samples. After oncology team discussion, she was referred for chemotherapy with immunotherapy (carboplatin, etoposide, atezolizumab). The first treatment cycle was given 20 days after admission to the hospital with her first symptoms. During treatment, she had 2 epileptic seizures, loss of recent memory, and disorientation. After MRI and cerebrospinal fluid analysis, drug-induced (atezolizumab) autoimmunologic encephalitis was diagnosed. There were severe metastases to the central nervous system and to other organs. The patient was gradually deteriorating neurologically and died due to sepsis 8 months after diagnosis (Table 1).

Figure 2.

Chest X-ray. A large mass in the middle region of left lung interflowing with enlarged left hilum (1).

Figure 3.

Chest CT. A spiculated tumor in the left lung hilum (1).

Figure 4.

Bronchoscopy. An exophytic tumor closing bronchus LB3 (1).

Discussion

The coexistence of lung cancer with COPD has received increasing attention in recent years. These 2 entities are attributed to older age, with a mean age around 70 years [3]. Here, we present 3 fatal cases of lung cancer and COPD in relatively young patients. To the best of our knowledge, only about 10% of patients diagnosed with lung cancer or COPD are under 55 years old, and less than 2% have coexistence of both diseases [4–8]. COPD in people younger than age 40 is extremely rare. The genetic mutation (alpha-1 antitrypsin deficiency) is strongly associated with the beginning of COPD in young patients [9].

Lung cancer diagnosis is often delayed in young people, but the same symptoms in older patients would clearly suggest lung cancer and accelerate diagnosis and treatment. Our patients were diagnosed only after acute illness or in the hospital departments, with long-lasting symptoms. The best outcomes occur when the diagnosis of lung cancer is made in asymptomatic patients and in the early cancer stage, which allows for radical treatment and significantly increases survival. In Patient 1, the late diagnosis was caused by susception of an infection, which postponed lung cancer diagnosis. In Patient 2, the late diagnosis was caused by the coexistence of pneumonia, which is why there was no diagnostic first bronchoscopy. She would have been a good candidate for radical surgery, which can be curative [10]. Patient 3 was very quickly diagnosed after the first symptoms occurred, treatment was started immediately, and she was young and in good general condition; however, her lung cancer was in an advanced stage and did not respond well to the treatment. She died within a few months with immunotherapy complications and progression of disease.

The most significant problem of young patients with coexistence of COPD and lung cancer is late diagnosis. In younger patients, symptoms are rarely attributed to possible lung cancer. Secondly, in patients with COPD, the COPD symptoms can mask some of the new lung cancer symptoms. These factors can delay diagnosis of lung cancer [11]. Delayed diagnosis of either of these 2 diseases and suboptimal treatment can lead to death. All of our 3 patients were heavy smokers, which is the main risk factor for developing COPD and lung cancer. All of them may have benefitted from LDCT in an asymptomatic period of lung cancer disease. Radiation with modern CT is relatively low, and costs of effective screening is much less than treatment of lung cancer and subsequent comorbidities. The most powerful therapeutic approach for NSCLC is surgical lung resection, which is possible mainly in stages I, II, and IIIa. Young patients are usually good candidates for radical surgery because of their good general condition [2]. Screening using LDCT significantly reduces mortality due to lung cancer, and several scientific societies now recommend this technique, usually in patients above 50–55 years old [12,13]. The discussion on modifications of indication to LDCT is ongoing [14]. It is currently under discussion if the screening should be performed in patients younger than 50 years old, and our study supports the need for this modification.

The coexistence of COPD, especially emphysematous COPD, decreases survival of patients with lung cancer, regardless of histological type of cancer, as revealed by most studies [15]. In 2 of our cases, COPD was diagnosed during diagnosis of lung cancer. Early spirometry in the asymptomatic period can lead to early COPD diagnosis and would be beneficial for all patients. Proper COPD treatment, which avoids exacerbations, is known to increase survival and extend life. It is so important to have oncological vigilance and perform regular spirometry in younger smokers aged 40–55 years old who present symptoms like cough, dyspnea, or tiredness, or do not present any symptoms. Despite being young, our 3 patients had low spirometric parameters. Spirometry is not included in the most recently GOLD recommendation for COPD qualification, but our results show the usefulness of pulmonary function testing, which is especially useful during qualification to bronchoscopy and, if possible, surgical treatment.

Conclusions

Lung cancer and COPD are diseases attributed to older age, but should not be forgotten in younger patients. Moreover, oncologic vigilance is needed, especially in heavy smokers, patients with pneumonia, atypical pulmonary infection, or cough, even if these symptoms are presented by younger patients. Lastly, we strongly emphasize the need for extension of the criteria for screening for lung cancer and COPD for young smokers.