Pulmonary rehabilitation: a unfairly forgotten therapeutic tool even in the worst scenarios

INTRODUCTION

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect almost every organ or system. Pleuropulmonary involvement, often underdiagnosed, occurs in about 60-80% of SLE cases¹. Shrinking lung syndrome (SLS) is one of its rare, although debilitating, complications occurring between 0.5-1.1% of patients². It is characterized by progressive unexplained dyspnea, chest pain, elevated hemidiaphragm, and reduced lung volumes with restrictive pattern on pulmonary function tests (PFTs), but without parenchymal anomalies². Despite being more prevalent during the later stages of the disease, it can manifest at any stage of SLE, even with inactive disease (in more than half of patients, according to SELENA-SLEDAI scores) and usually without prior or simultaneous involvement of other organs³.

It has been rarely described in other autoimmune disorders and is more prevalent in women (with ratio 6:1)³. Differential diagnoses include restrictive respiratory defect due to pulmonary fibrosis, obesity, diaphragmatic palsy, and central nervous system disorders⁴. There are no definite criteria for SLS diagnosis, and it usually relies on the association of reduced lung volumes and restrictive defects on PFTs, together with the exclusion of other causes⁴.

Even though its pathophysiology remains unknown, because pleuritic chest pain is a prominent feature of SLS, it has been hypothesized that pleural effusion and inflammation could reduce diaphragmatic mobility. This would inhibit deep inspiration, resulting in chronic lung hypo-inflation, consequently leading to parenchymal remodeling with changes in elasticity and decrease in lung compliance^5,6.

Although the therapeutic approach does not gather consensus, the first-line treatment usually includes corticosteroids with or without immunosuppressants^1,2. In their review, Duron et al. concluded that there was no prognostic difference between patients receiving isolated steroids or steroids associated with immunosuppressants⁴. Theophylline and beta-agonists alone or in combination with glucocorticoids have been also employed to increase diaphragmatic strength^7,8. Although the SLS mechanism is poorly understood, there have also been positive outcomes with rituximab and belimumab as B cells may play an important role in SLS pathophysiology^9,10.

Surprisingly, no published literature on SLS patients makes any consistent reference to the benefits of respiratory pulmonary rehabilitation programs as a crucial component of any chronic lung disease management.

DESCRIPTION

The authors present the case of a 57-year-old female, with past medical history significant for SLE with 12 years duration, secondary antiphospholipid syndrome, and chronic pulmonary embolism. In a routine consultation, she had complains of progressive worsening of dyspnea on minor exertion (mMRC grade 2) and intermittent pleuritic chest pain over the past four months, with no extra-thoracic manifestations of SLE, namely, arthralgia or cutaneous involvement. At that time, her therapy consisted of daily prednisolone 10 mg/day, hydroxychloroquine 400 mg/day in addition to azathioprine 50 mg thrice a day, formoterol twice a day, and rivaroxaban 20 mg/day.

The chest X-ray showed small lungs and bilateral elevation of the diaphragm, with no evidence of pleuroparenchymal changes. For better clarification, the patient underwent chest computed tomography to assess the eventual pulmonary involvement. As shown in Figure 1, there were only residual linear opacities compatible with fibrotic bands/linear atelectasis with no other relevant parenchymal findings, nor pleural effusion, as commonly reported in SLS cases¹¹. Fluoroscopy showed bilateral diaphragmatic paralysis. PFTs confirmed a restrictive ventilatory defect with her forced vital capacity (FVC) being 60.4% of predicted, low total lung capacity (TLC) being 60.3% of predicted, forced expiratory volume (FEV1) being 61.2% of predicted, functional residual capacity (FRC) being 59.8% of predicted, residual volume (RV) being 58.4% of predicted, reduced diffusing capacity for carbon monoxide (DLCO) being 56.8% of predicted, transfer coefficient of the lung for carbon monoxide (KCO) being 91.7% of predicted, and resting gas exchange without significant difference from the age predicted pO₂ being 80.3 mmHg. A 6-min walk test was performed, but the patient only tolerated two min due to excessive dyspnea and desaturation (completed only 142 m; 96-84% oxygen desaturation; maximum exertion on Borg Scale 10/10). Despite having an adequate cardiac response to effort on cardiopulmonary exercise testing (CPET), she presented an important ventilatory limitation (VO₂ 17.8 mL/min/kg, 62% of predicted), as her respiratory reserve was depleted, due to a gas exchange compromise with consequent desaturation, probably potentiated by her pulmonary vasculopathy; subsequent lung ventilation-perfusion (V/Q) scintigraphy confirmed evidence of chronic pulmonary thromboembolism, although without pulmonary hypertension, and she began full dose rivaroxaban. As reported elsewhere, there was an unusual C-reactive protein elevation, not common on controlled SLE¹². Considering all these results, SLS diagnosis was assumed, and she initiated aminophylline thrice a day. Noteworthy, as shown in Table 1, when aminophylline was discontinued due to iatrogenic tachycardia, the patient reported worsening of shortness of breath concomitantly with marked decline of her restrictive lung pattern (FVC=36.2%; TLC=40.7%; FEV1=40.3%; FRC=36.7%; RV=46%, of the predicted values). Despite increasing corticosteroid and azathioprine doses, her tolerance to efforts continued to diminish, and she was started on a pulmonary rehabilitation program, twice weekly, for the next five months. The patient performed aerobic exercise training, ventilatory control exercises, and strength training of the upper and lower limbs. She presented a progressive improvement in exercise tolerance with endurance testing showing a significant increase in exercise tolerated time (from 9:25-30 min). The respiratory complains as well as the sequential PFT of patient began to improve progressively (Table 1). At present, her mMRC is grade 1, TLC is 51.6% of predicted, and she completes 462 m on the 6-min walk test, considered a minimal clinically important difference (MCID)¹³ with 97-91% oxygen saturation and a Borg Scale 3/10. She is currently maintained on azathioprine 200 mg twice a day and prednisolone 5 mg/day, after a gradual weaning period; aminophylline was also carefully reintroduced. Equally important as exertional tolerance is the unquestionable improvement of patient’s quality of life, being now able to restore her professional and normal activities of daily living (ADL), as expressed on The London Chest ADL Scale (LCADL)¹⁴ which score diminished from 26-17, also considered MCID. Furthermore, on the Hospital Anxiety and Depression Scale (HADS)¹⁵, there was also a favorable evolution of clinical importance (Table 1).

Figure 1.
Chest computed tomography shows elevated hemidiaphragms with reduced lung volume, residual linear opacities compatible with fibrotic bands/linear atelectasis in medium lobe, anterior segment of the left upper lobe and lower lobes; right accessory tracheal bronchi directing toward the right upper lobe, with no other parenchymal relevant findings.

Table 1.
Evolution of the most important parameters.

	Before pulmonary rehabilitation	After aminophylline discontinuation	After pulmonary rehabilitation
FVC (% of predicted)	60.4	36.2	49.7
FEV1 (% of predicted)	61.2	40.3	54.2
TLC (% of predicted)	60.3	40.7	51.2
RV (% of predicted)	58.4	46	60.6
DLCO (% of predicted)	56.8	**	**
KCO (% of predicted)	91.7	**	**
pO2 (mmHg)	80.3	77.4	77.5
VO2 (ml/kg/min; % of predicted)	17.8 (62)	-	-
6-min walk test (m)	142	-	462*
Exercise tolerated time (min)	9:25	-	30*
Borg Scale	10	10	3
mMRC	2	3	1
LCADL	26	-	17*
HADS	16	-	12*

• FVC: forced vital capacity; TLC: low total lung capacity; FEV1: forced expiratory volume; RV: residual volume; DLCO: reduced diffusing capacity for carbon monoxide; KCO: transfer coefficient of the lung for carbon monoxide; mMRC: modified medical research council dyspnea scale; LCADL: the London chest activities of daily living scale; HADS: hospital anxiety and depression scale. *Considered minimal clinically important difference (MCID). **Not calculated because of low volumes.

CONCLUSIONS

Shrinking lung syndrome is a rare lupus pulmonary manifestation of uncertain etiology whose diagnosis relies on the association of restrictive pulmonary capacity without interstitial lung disease, pleural effusion, or phrenic nerve palsy. Dyspnea, pleuritic chest pain, and elevated diaphragm should raise suspicion for this diagnosis¹⁶. In most cases, it has a favorable long-term prognosis if detected early and treated properly to avoid irreversible restrictive disturbances sequelae; however, in some case series, only 20% of patients normalize pulmonary function^9,16, while rest of them show only functional improvement or even stabilization of lung function¹⁷.

This case report is noteworthy, not only due to the rarity of this syndrome and the clear advantages of multidisciplinary management, but also essentially to stress out the core importance of pulmonary rehabilitation as a non-pharmacological tool that unquestionably reinforces therapeutic armamentarium not only on lupus shrinking lung syndrome but also on any chronic lung disease.

REFERENCES

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• Funding: none

Publication Dates

• Publication in this collection
  15 Oct 2021
• Date of issue
  June 2021

History

• Received
  14 Apr 2021
• Accepted
  02 May 2021