Impact of bronchoalveolar lavage lymphocytosis on the effects of anti-inflammatory therapy in idiopathic non-specific interstitial pneumonia, idiopathic pleuroparenchymal fibroelastosis, and unclassifiable idiopathic interstitial pneumonia

Abstract

Background Idiopathic non-specific interstitial pneumonia (iNSIP), idiopathic pleuroparenchymal fibroelastosis (iPPFE), and unclassifiable idiopathic interstitial pneumonia (IIP) are IIPs with chronic fibrotic phenotypes, and unlike idiopathic pulmonary fibrosis, they have often been treated with anti-inflammatory drugs, including corticosteroids and immunosuppressants. However, the impact of bronchoalveolar lavage (BAL) lymphocytosis on the effects of anti-inflammatory therapy has never been evaluated. This study aimed to elucidate whether BAL lymphocytosis can be used to predict the efficacy of anti-inflammatory drugs for iNSIP, iPPFE, and unclassifiable IIP. Methods Japanese patients diagnosed with iNSIP, iPPFE, and unclassifiable IIP by multidisciplinary discussion were identified using the nationwide registry. Eligible patients were stratified into four groups with and without BAL lymphocytosis and anti-inflammatory therapy to compare overall survival (OS) and changes in lung function. BAL lymphocytosis was defined as a lymphocyte differential count > 15%, and the cut-off was corroborated by survival classification and regression tree analysis. Results Overall, 186 patients (37 iNSIP, 16 iPPFE, and 133 unclassifiable IIP) were analyzed. Limited to patients treated with anti-inflammatory drugs (n = 123), patients with BAL lymphocytosis had a better prognosis [hazard ratio (HR), 0.26; 95% confidence interval (CI), 0.11–0.63; P = 0.003], higher slope of forced vital capacity (FVC) % predicted for 2 years, and longer OS (log-rank test, P = 0.012) than those without BAL lymphocytosis. On multivariate analysis, BAL lymphocytosis (HR 0.31; 95% CI 0.13–0.75; P = 0.009) was a prognostic factor for OS, along with age and FVC % predicted. Conversely, for patients managed without anti-inflammatory therapy (n = 63), the presence or absence of BAL lymphocytosis had no prognostic value. Conclusions BAL lymphocytosis is associated with good outcomes in patients treated with anti-inflammatory drugs, but has no prognostic value when anti-inflammatory drugs are not used. BAL lymphocytosis may provide a predictive biomarker for identifying patients with iNSIP, iPPFE and unclassifiable IIP who are likely to benefit from anti-inflammatory drugs.

Clinical characteristics and prognostic factors of fibrotic nonspecific interstitial pneumonia

“… 5 , 6 , 27 Given that progression and relapse are associated with grave outcomes, the identification of their predictive factors is important for improving outcomes. Several multicenter survey studies have suggested the presence of ANA, low BAL lymphocyte count (⩽15%), or long duration of symptoms as possible risk factors for unresponsiveness to treatment in fibrotic ILD or idiopathic NSIP; 28 , 29 however, the predictive factors for progression or relapse in fibrotic NSIP have not been established. To the best of our knowledge, this is the first study to investigate the risk factors for progression or relapse in biopsy-confirmed fibrotic NSIP based on distinct criteria.…”

Pharmakotherapie der idiopathischen Lungenfibrose (ein Update) und anderer progredienter pulmonaler Fibrosen

“…In der Studie von Yamagata et al war eine BAL-Lymphozytose < 15 % ein unabhängiger negativer Prädiktor für das Ansprechen auf antiinflammatorische Therapie 104 . In einer retrospektiven Studie bei 91 Patienten mit fibrotischer EAA war eine BAL-Lymphozytose < 20 % gemeinsam mit Honigwabenmuster im HRCT mit fehlendem Ansprechen auf die Steroidtherapie assoziiert 117 .…”

“…Bei vielen Erkrankungen nimmt sie mit fortschreitender Fibrosierung eher ab. Eine retrospektive Studie aus Japan zeigte bei Patienten mit chronisch fibrotischen ILDs (37 iNSIP, 16 iPPFE, 133 unclassifiable IIP), dass eine BAL-Lymphozytose nur bei den antiinflammatorisch behandelten Patienten mit einer günstigeren Prognose assoziiert war, nicht jedoch bei den unbehandelten Patienten 104 .…”

“…In der Studie von Yamagata et al war eine BAL-Lymphozytose < 15 % ein unabhängiger negativer Prädiktor für das Ansprechen auf antiinflammatorische Therapie [104]. In einer In die Entscheidung zur antiinflammatorischen Behandlung der autoimmunen ILD soll die Art der zugrundeliegenden rheumatologischen Erkrankung einfließen.…”

S1-Leitlinie Interdisziplinäre Diagnostik interstitieller Lungenerkrankungen im Erwachsenenalter

“…darauf hinweisen, dass die Krankheit auf anti-inflammatorische Therapie ansprechen bzw. eine günstige Prognose aufweisen wird [104][105][106]. Bei Patient:innen mit systemischen Autoimmunkrankheiten korreliert eine leicht-bis mittelgradige Neutrophilie eher mit fortgeschrittener fibrotischer ILD [107].…”