Abstract
Shrinking lung syndrome is a rare complication of systemic lupus erythematosus; its impact on sleep-disordered breathing is not well understood. We describe a case of a 36-year-old female with systemic lupus erythematosus experiencing shrinking lung syndrome and frequent pain crises. We review manifestations of her disease during non-rapid eye movement (NREM) and rapid eye movement sleep. Shrinking lung syndrome with its restrictive physiology and associated diaphragmatic myopathy is expected to decrease minute ventilation during NREM and rapid eye movement sleep. Normalization of respiratory rate during NREM, as opposed to rapid eye movement and awake state, should alert clinicians to dysfunctional breathing that is suppressed in NREM when cortical breathing is overridden by involuntary breathing. Recognition of dysfunctional breathing disorders by sleep providers is important for addressing all contributors to dyspnea in patients with systemic lupus erythematosus; polysomnogram can be a valuable tool in detecting incongruent ventilation parameters that deviate from expected NREM and rapid eye movement norms and point to dysfunctional breathing disorders. Abnormalities in respiratory rate and gas exchange that improve or vanish in NREM sleep can serve as an additional diagnostic clue of dysfunctional breathing disorders.
Citation:
Saleh D, Loewen A. Shrinking lung syndrome: vanishing in non-rapid eye movement sleep. J Clin Sleep Med. 2023;19(11):1975–1979.
Keywords: shrinking lung syndrome, NREM, REM, dysfunctional breathing disorder, sleep medicine
INTRODUCTION
Shrinking lung syndrome (SLS) is a rare complication of systemic lupus erythematosus (SLE) whereby patients experience dyspnea and pleuritic chest pain accompanied by reduction in lung volume in the absence of parenchymal abnormalities on radiographic imaging.1,2 The reported prevalence of SLS is 0.5%–1.1%1–3; it is usually suspected in symptomatic patients with connective tissue disease and progressive extraparenchymal lung restriction on spirometry with elevation of hemidiaphragms.2,3 Several pathophysiological mechanisms have been hypothesized in SLS; these include pleural inflammation and pain limiting deep inspiration and resulting in underinflation with decreasing lung compliance, pleural adhesions, diaphragmatic myopathy, surfactant deficiency, and phrenic nerve lesions.1–4 While poor quality sleep and obstructive sleep apnea have been described in SLE, larger, more rigorous studies describing manifestations of sleep-disordered breathing in patients with SLE are lacking.5
We hypothesize that pleural inflammation and pain in select patients with SLS can contribute to dysfunctional breathing disorder (DBD). DBD is defined as the sensation of dyspnea accompanied by an irregular breathing pattern such as hyperventilating or periodic deep sighing that is not explained by respiratory or cardiac pathologies and is a diagnosis of exclusion.6 While DBD has been observed in conditions such asthma and panic attacks,6 the prevalence of DBD in patients with SLE, particularly in those experiencing pain crises, remains unknown.
REPORT OF CASE
A 36-year-old female with longstanding SLE complicated by multiple pain crises and SLS presented to the sleep clinic for sleep-disordered breathing screening after her sitting forced vital capacity measured at 1.12 L (32%, predicted), with a positional drop of 30% in forced vital capacity from sitting to supine. Imaging demonstrated bilateral elevated hemidiaphragm without evidence of parenchymal abnormality; fluoroscopy confirmed absence of diaphragm movement bilaterally with deep breathing. Her echocardiogram showed an elevated right ventricular systolic pressure of 42 mmHg with evidence of moderate to severe mitral regurgitation. See Table 1 for complete spirometric data. She was on hydroxychloroquine, prednisone, and azathioprine.
Table 1.
Baseline spirometric and plethysmography data.
| Spirometric and Plethysmography Data | Value |
|---|---|
| BMI | 19 |
| FEV1/FVC | 0.91 |
| FVC | 1.12 L, 32%, predicted |
| TLC | 2.58 L, 52% of predicted |
| DLCO | 7.35 ml/min/mmHg, 30% of predicted |
| D/VAsb | 4.43 ml/min/mmHg, 94% of predicted |
| Maximal inspiratory pressure | −35 cm H2O, 38% of predicted |
| Maximal expiratory pressure | + 45 cmH2O, 45% of predicted |
BMI = body mass index, DLCO = diffusing capacity of the lungs for carbon monoxide, D/VAsb = DLCO divided by single-breath alveolar volume, FEV1 = forced expiratory volume in 1 second, FVC = forced vital capacity, TLC = total lung capacity.
She underwent diagnostic polysomnogram, which demonstrated a normal apnea-hypopnea index of 1.3 and relative hypoventilation with elevation in transcutaneous carbon dioxide by more than 10 mmHg in rapid eye movement (REM) sleep in comparison to non-rapid eye movement (NREM) values. Decreased tidal volume (VT) and oxygen saturation during awake state and REM sleep with marked improvement in these parameters during NREM sleep was also observed (see Table 2 for comparison; Figure 1, Figure 2 and Figure 3 outline epochs where such changes were observed.). These values were discordant from the normal progression of decreasing minute ventilation from wakefulness to NREM to REM sleep seen in healthy individuals.7
Table 2.
Comparison of various ventilatory parameters during awake state, NREM, and REM sleep.
| Awake | NREM N2 | REM | |
|---|---|---|---|
| Diagnostic | Diagnostic | ||
| TCO2 | 53 mmHg | ⇓ 42 mmHg | 50–54 mmHg |
| RR | ⇑ ⇑ ⇑ (20 breaths/min) | ⇓ (14 breaths/min) | ⇑⇑⇑ (24 breaths/min) |
| SPO2 | 90%–93% | 92%–94% | 87% |
NREM = non-rapid eye movement, REM = rapid eye movement, RR = respiratory rate, SPO2 = peripheral oxygen saturation, TCO2 = transcutaneous carbon dioxide, VT = tidal volume.
Figure 1. 60-second epoch in awake state showing hyperventilation with hypercapnia.
Figure 2. 60-second epoch in non-rapid eye movement sleep showing improved transcutaneous carbon dioxide levels and respiratory rate.
Figure 3. 60-second epoch in rapid eye movement sleep showing desaturation and hypoventilation.
DISCUSSION
Normally, reduction in respiratory rate (RR) and decreased oxygen and carbon dioxide (CO2) chemosensitivity leads to reduced minute ventilation in NREM sleep, particularly in slow-wave sleep, and increases CO2 levels by 1–2 torr.7,8 REM sleep is characterized by variability in RR and VT and a decreased ventilatory response to CO2, further elevating CO2 by 5–6 torr.7 However, REM sleep has been termed paradoxical sleep by Michel Jouvet, since a waking electroencephalogram is observed during behavioral sleep and breathing patterns (variability in RR and VT) approximate wakefulness more than in NREM.9 The discordance in ventilatory parameters in our patient from what is observed in the normal wake state and NREM sleep raised the possibility of an alternative explanation from neuromuscular disorders for her tachypnea and dyspnea.7
Patients with neuromuscular disorders recruit inspiratory accessory muscles during NREM and REM sleep to compensate for intercostal and diaphragmatic muscle weakness10; they develop progressive hypoventilation and nocturnal desaturation during sleep that is most profound in phasic REM.10–12 For this reason, improvement in CO2 and oxygen levels of our patient in NREM sleep argues against neuromuscular disorders. See Table 3 for comparison of ventilatory parameters during sleep stages between healthy individuals and those with neuromuscular disorders with impaired respiratory mechanics.10–12 One hypothesis that could explain the observed ventilatory changes in our patient is that DBD in the context of pleuritic chest pain was suppressed in NREM due to loss of cortical breathing control, leading to improvement in oxygenation and ventilation compared to wake state and REM. This observation can serve as a diagnostic clue to help differentiate cases of DBD from other cases of restrictive lung physiology where RR remains elevated and minute ventilation decreases in NREM sleep.7,12
Table 3.
Comparison of various ventilatory parameters during awake state, NREM, and REM sleep between healthy individuals and those with NMD with impaired respiratory mechanics.8,10–12
| Awake | NREM | Tonic REM | Phasic REM | |||||
|---|---|---|---|---|---|---|---|---|
| Healthy | NMD | Healthy | NMD | Healthy | NMD | Healthy | NMD | |
| RR | N (12–18 breaths/min) | ⇑ | ⇓ in N2 ⇑ in N3 | ⇓⇓ | ⇑ | ⇑ or ⇒ | ⇑⇑ | ⇑ or ⇒ |
| VT | N (∼500 ml) | ⇓ | ⇓ | ⇓⇓ | ⇓ or ⇒ | ⇓⇓ | ⇓⇓ | ⇓⇓⇓ |
| TCO2 | N (35–45 mmHg) | N in early disease ⇑ in later stages | N | ⇑⇑ | N or slightly ⇑ | ⇑⇑⇑ | ⇑ | ⇑⇑⇑ |
| SPO2 | N (90%–100%) | N or ⇓ | N | ⇓⇓ | N or slightly ⇓ | ⇓⇓⇓ | N or slightly ⇓ | ⇓⇓⇓ |
⇒ = unchanged, N = normal, NMD = neuromuscular disorders, NREM = non-rapid eye movement, REM = rapid eye movement, RR = respiratory rate, SPO2 = peripheral oxygen saturation, TCO2 = transcutaneous carbon dioxide, VT = tidal volume.
This case suggests a possible interplay between pain and DBD that can decrease lung expansion and contribute to relative hypoventilation in wakefulness and REM. While there are no large studies reporting on the prevalence of DBD in patients with SLE, it can be postulated that inflammatory pleural pain during deep inspiration may result in shallow breathing; this coupled with peripheral neuropathies in SLE may result in thoraco-abdominal asynchrony leading to dysfunctional breathing that manifests as hypoventilation and desaturation in the awake state and REM.4,6
While many cases of SLS are published in the literature,1–3 this is a unique case suggesting a possible correlation between DBD and SLS as an alternative mechanistic etiology of hypoventilation in patients with SLE. Further research is needed to understand the complex interplay between pain, DBD, and physiological responses in sleep. Although not completed in this case, further investigation of this hypothesis could be by performing cardiopulmonary exercise testing as patients with SLE have been shown to have ventilatory inefficiency with decreased VT, higher RR to VT ratio, and an elevated ventilatory equivalent for CO2.13 Given the pain and potential diaphragmatic myopathy in patients with SLS, arm crank ergometry can perhaps be employed to reduce patient workload, allowing for longer exercise time to detect ventilatory responses to incremental exercise.14
DISCLOSURE STATEMENT
All authors have seen and approved the case report. The authors report no conflicts of interest.
ABBREVIATIONS
- CO2
carbon dioxide
- DBD
dysfunctional breathing disorder
- NREM
non-rapid eye movement
- REM
rapid eye movement
- RR
respiratory rate
- SLE
systemic lupus erythematosus
- SLS
shrinking lung syndrome
- VT
tidal volume
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