Introduction

High-resolution computed tomography (HRCT) scanning has enhanced recognition of the simultaneous occurrence of emphysema and pulmonary fibrosis and, recently, combined pulmonary fibrosis and emphysema (CPFE) has been defined as a syndrome. This syndrome is characterized by upper lobe emphysema and lower lobe fibrosis [1]. Common risk factors resulting in epithelial lung alterations may contribute to emphysema and pulmonary fibrosis despite clinical, radiological, and pathologic differences [2-4]. Coexistence of emphysema and fibrosis are more likely to occur in smoking-induced parenchymal pulmonary damage [5,6]. CPFE is still under-diagnosed and clinical management as well as therapeutic approaches have not yet been clearly defined. In this case we explore the potential benefits of a specific aerobic physical retraining program, which has not yet been considered within the therapeutic options for CPFE.

Case presentation

We report the case of a 65-year-old Caucasian man who had previously smoked cigarettes (40 pack-years) who had CPFE with several comorbidities, including hypertension, type II diabetes, and depression. Before his CPFE diagnosis our patient had been affected by chronic bronchitis for 12 years. His diagnosis of CPFE was confirmed by thoracic HRCT showing areas of intralobular interstitial and septal thickening with peripheral bilateral distribution in addition to centrilobular emphysema of both his upper lobes. On admission to our rehabilitation clinic, our patient exhibited chronic respiratory failure, reporting dyspnea on exertion and productive cough; our patient was receiving long-term oxygen therapy (LTOT) with 2.5L/min of flow during 24 hours as his peripheral capillary oxygen saturation (SpO2) steeply declined when oxygen therapy was discontinued (SpO2= 84%). Spirometry showed a relatively mild restriction although his diffusion lung capacity for carbon monoxide (DLCO) was 44% of predicted. Concurrent pulmonary hypertension (PAP 60mmHg) was diagnosed by color doppler echocardiography.

Our patient’s pharmacological therapy consisted of high dose inhaled steroids, acetyl-cysteine 1200mg once daily, angiotensin-converting-enzyme inhibitor (Lisinopril) 10mg once daily, and aspirin 100mg once daily. Respiratory and physical exercise test assessments were carried out at admission and discharge; in addition, quality of life (St. George Respiratory) and depression level (Geriatric Depression Scale) questionnaires were administered by a clinical psychologist. Our patient performed the six-minute walk test (6MWT) to evaluate his aerobic physical performance according to the European Respiratory Society/American Thoracic Society recommendation, 2014. The test was performed by an exercise physiologist indoors, along a long, flat, straight, enclosed corridor with a hard surface of 30 meters, and results reported as distance (meters) covered in six minutes. His usual medical regimen was continued and oxygen therapy during the test was administered via a portable oxygen tank. As required by standard protocol, our patient decided the speed of the walk, stopping as required and resuming the test when recovered. Before, during, and after the test, his heart rate and oxygen saturation were reordered using a professional oximeter, and dyspnea levels and overall fatigue were assessed according to the Borg Scale and Visual Analogue Scale (VAS) before and immediately after exercise test. After two weeks in our rehabilitation unit, our patient was clinically stabilized and enrolled in the retraining program for four weeks. The retraining program took place in the cardiorespiratory gymnasium of our rehabilitation unit. Written consent was obtained from our patient before starting the exercise program.

Each retraining session was supervised by an exercise physiologist monitoring heart and respiratory rate, oxygen saturation, blood pressure, and level of dyspnea. Our patient underwent the exercise program for two sessions per day up to 30 minutes each, five days per week, for a four-week period. The training included one session of aerobic exercise and one session of breathing technique. For aerobic training, he exercised on a treadmill, with a speed of 2.5km per hour and 0% of slope. The intensity of aerobic exercise was adapted to our patient’s functional capacity on the basis of his 6MWT results, in accordance with aerobic exercise intensity recommended by American Thoracic Society Guidelines 2006 for pulmonary rehabilitation. Therefore, the work rate of training corresponded to 50% to 60% of his maximum heart rate and the training began at a work rate equal to 50%. When our patient reached the level of exercise at 10 minutes without intolerable dyspnea (Borg rating of breathlessness of <5), the workload (speed and/or elevation) and duration of exercise were increased by 10% [7]. Progressive exercise training was employed for his respiratory muscles; the training consisted of diaphragmatic breathing and inspiratory muscle training, through an inspiratory threshold, at 40% to 50% of his initial maximal inspiratory pressure (PiMax). During training our patient received oxygen therapy to maintain SpO2 >92%; a flow reduction of 15% was made each week.

After the four-week retraining program, because his arterial blood gas analysis showed a PaO2 increase of 11% and PCO2 decrease of 5.6% on oxygen with a flow of 2.5L/min, it was possible to reduce his LTOT to a flow of 1.5L/min for 24 hours to compensate hypoxemia. The oxygen requirement reduction observed may have been due to the strengthening of his respiratory muscles, which allowed improvement of his exercise capacity [8]. His pulmonary artery systolic pressure, estimated by transthoracic two-dimensional echocardiography, improved by 16% in terms of cardiac index and pulmonary vascular resistance [9]; no significant lung function changes were observed. Relevant improvements in exercise capacity, dyspnea rating, health-related quality of life, and levels of depression were also demonstrated after the pulmonary rehabilitation program. His 6MWT showed an increase of distance walked by 133%. His dyspnea scores were reduced: the level of dyspnea at rest (the Modified Medical Research Council Dyspnea Scale) decreased from 3.0 to 2.0, Borg Scale during exercise was reduced from 9.0 to 5.0, and his post-exercise VAS decreased from 8.0 to 5.0; there was only a minor increase in PiMax of 17%. Our patient’s adherence to the retraining program was good and no adverse events occurred. Table 1 reports the test results collected before and after the retraining program.

Table 1 Results of cardiorespiratory and clinical tests before and after a retraining program in a patient with combined pulmonary fibrosis and emphysema
Full size table

Discussion

In this case study we evaluated whether a patient with CPFE, a disease which has not yet been considered for pulmonary rehabilitation, can benefit from an aerobic retraining program. Emphysema and pulmonary fibrosis are progressive lung diseases that may be associated with comorbidities and systemic consequences [10-14]. CPFE syndrome typically occurs in male smokers and is frequently complicated by pulmonary hypertension, acute lung injury, and lung cancer, which affect disease progression and survival. In the literature there are no reports on the efficacy of physical retraining in patients with CPFE, in contrast with other lung diseases such as chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis where clinical studies have demonstrated the benefits of pulmonary rehabilitation [15]. Clinically relevant improvements and short-term benefits were clearly demonstrated in this report as a result of a retraining program. Although clinical studies on long-term effects within a large patient population are required for definitive conclusions, our observations suggest that integrating pulmonary rehabilitation with pharmacological treatments would be beneficial for patients with CPFE.

Conclusions

In the literature there are no reports on the effects of pulmonary rehabilitation in patients with CPFE. The potential efficacy of aerobic exercise on quality of life and psychological well-being and exercise capacity function in a patient with CPFE has been demonstrated in this case. Our results suggest that exercise should also be considered as a therapeutic option for patients with CPFE, although further studies considering the impact of different types of training in this patient population are required.

Consent

Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal.