The patient was an 81-year-old woman. Around June 2012 she noticed difficult breathing while walking; then as the symptom worsened she visited our hospital in October 2012. In December of the same year, bronchoscopy together with bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) were performed. The dominant cells in BAL fluid were monocytes, and TBLB demonstrated mild lymphocyte infiltration and fibroblast hyperplasia. Respiratory function tests showed restrictive lung disorder with a percentage vital capacity (%VC) of 63.0%, forced vital capacity (FVC) of 1.05 L, percentage forced vital capacity (%FVC) of 55.5%, forced expiratory volume in one second (FEV1) of 1.05 L, percentage of predicted forced expiratory volume in one second (FEV1%) of 107.1%, and percentage of forced expiratory volume in one second (Gaensler's FEV1%) of 100.0%. Computed tomography (CT) showed honeycombing along with traction bronchiectasis in the subpleural and basal areas of both lungs (Fig. 1a). Findings of physical examination and blood tests showed no evidence of collagen-vascular disease or any other condition apart from idiopathic pulmonary fibrosis. Thus, based on clinical findings, the patient was diagnosed idiopathic pulmonary fibrosis (IPF). In addition, the transthoracic echocardiography showed a tricuspid regurgitation (TR) pressure gradient of 31.7 mmHg and a pulmonic regurgitation (PR) pressure gradient of 6.2 mmHg.
The patient was started on oral pirfenidone in February 2013, but this was discontinued in October 2013 because of difficulty taking oral medication. As for imaging examinations, in August 2013 these ruled out progression of IPF, but the patient showed aggravation of dyspnea and decreased oxygen saturation, as well as onset of orthopnea and rapidly progressing edema. Transthoracic echocardiography demonstrated findings consistent with congestive heart failure secondary to pulmonary hypertension (PH), and thus the patient was started on diuretic therapy. However, her condition showed little improvement and the patient was thus hospitalized for detailed examination and treatment in October 2013. Findings of physical examination upon admission included body temperature 36.9  C, blood pressure 94/52 mmHg, regular heart rate at 95 beats per minute, respiratory rate 25 breaths per minute, oxygen saturation 80% (on oxygen 3 L/min by nasal cannula), engorged jugular veins on inspection, and bilateral crepitations on auscultation.
Exacerbation of IPF was unlikely because the only significant finding from imaging examination and blood tests was elevated KL-6 that was attributed to influence of diuretic therapy given since before her admission and influence of congestion (Table 1 and Fig. 1b). In addition, after admission, transthoracic echocardiography and right heart catheterization were performed. The transthoracic echocardiographic finding suggested severe PH and a congestive condition (TR pressure gradient was 86.6 mmHg and PR pressure gradient was 16.1 mmHg total ejection isovolumetric (Tei) index was 0.44 and tricuspid annular plane systolic excursion (TAPSE) was 1.13 cm). (Fig. 2a).
Right heart catheterization showed systolic and diastolic pulmonary artery pressure (PAP) of 54 and 24 mmHg, respectively (mean PAP was 39 mmHg) and a systolic and diastolic pulmonary capillary wedge pressure (PCWP) of 16 and 0 mmHg, respectively (mean PCWP was 9 mmHg) (Table 2). After various examinations including lung perfusion scintigraphy that ruled out other diseases causative of PH, the diagnosis of PH due to IPF was established. Since treatments such as diuretic therapy and oxygen therapy do not improve circulatory failure associated with PH, on Day 12 of hospitalization the patient was started on oral bosentan at a dose of 125 mg/day, leading to rapid improvement of circulatory failure associated with PH. The dose of bosentan was increased to 250 mg/day from hospital Day 25 onward. After improvement of symptoms and findings, the patient was discharged from the hospital on long-term oxygen therapy (using Oxymizer ; dose of oxygen was 3 L/min at rest and 6 L/min on exertion) (Table 2). At the follow-up assessment one year later her pulmonary function showed no significant changes and no apparent worsening of arterial blood gases, with evident improvement of PH, WHO functional class, maximum exercise tolerance on treadmill exercise testing, right heart catheterization, and transthoracic echocardiography (Table 2 and Fig. 2b).
Chest roentgenogram and computed tomography (a). Chest roentgenogram and computed tomography at the initial visit Honeycombing along with traction bronchiectasis in the subpleural and basal areas of both lungs were detected.