
==== Front
BMC Pulm Med
BMC Pulm Med
BMC Pulmonary Medicine
1471-2466
BioMed Central London

3267
10.1186/s12890-024-03267-4
Research
Clinical features and risk factors for recurrence of idiopathic pulmonary hemosiderosis in children
Wang Lili 123
Li Yan 1
Zhang Rui 1
Liu Hanmin liuhm@scu.edu.cn

123
Chen Lina chenlina_78@163.com

123
1 grid.13291.38 0000 0001 0807 1581 Division of Pediatric Pulmonology and Immunology, West China Second University Hospital, Sichuan University, Chengdu, 610041 China
2 grid.419897.a 0000 0004 0369 313X Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, 610041 China
3 https://ror.org/011ashp19 grid.13291.38 0000 0001 0807 1581 NHC Key Laboratory of Chronobiology, Sichuan University, Chengdu, 610041 Sichuan China
19 9 2024
19 9 2024
2024
24 46111 2 2024
3 9 2024
© The Author(s) 2024
2024
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Background

This study aims to review the clinical characteristics, therapeutic response and outcome of idiopathic pulmonary hemosiderosis (IPH), and discover the risk factors for recurrence in children with IPH, which will be helpful for the early diagnosis and reasonable treatment of this disease.

Methods

Children with a diagnosis of IPH were enrolled in the study. Clinical data of the children were collected and analysed.

Results

A total of 32 patients with regular follow-up after diagnosis were included in this study. Anaemia, cough and haemoptysis constituted the most common initial symptoms of the disease, and the incidences were 90.6%, 75% and 56.2%, respectively. The mean gap between the onset of symptoms and diagnosis was 5 (0.25-36) months. Most of the children experienced remission (complete and partial remission) over the course of 6 months of treatment, but 19 of the children experienced relapse. The causes of disease recurrence included respiratory tract infection (37.5%), corticosteroid (CS) reduction (18.8%), and irregular medication (6.3%). Interestingly, we found that children with history of allergy (HR 4.255, 1.107–16.356) tended to experience disease recurrence (p = 0.01).

Conclusions

Cough and anaemia are the most common symptoms in children with IPH. The recurrence rate of this disease is high, and respiratory tract infection is the most common cause of its recurrence. High-dose CS impluse therapy cannot reduce the recurrence rate of the disease. Allergic history was an import factor associated with disease recurrence.

Trial registration

This study is a retrospective and observational study, which does not involve human specimens or clinical intervention. Therefore, clinical trial registration is not required, and there is no clinical trial number. However, the study was approved by the Institutional Review Board/Ethics Committee affiliated with West China Second University Hospital, Sichuan University (Ethics review number 2022074).

Keywords

Idiopathic pulmonary hemosiderosis
Children
Clinical characteristics
Risk factor
General Program of National Natural Science Foundation of China82370001 Fundamental Research Funds for the Central UniversitiesSCU2022D022 Development Fund for Clinical Discipline of West China Second Hospital of Sichuan UniversityKL118 Major Scientific and Technological Project from Science &Technology Department of Sichuan Province (2022ZDZX0021)issue-copyright-statement© BioMed Central Ltd., part of Springer Nature 2024
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pmcIntroduction

Idiopathic pulmonary hemosiderosis (IPH) is a rare but sometimes fatal disease in children, which is classically characterized by a triad of haemoptysis, iron-deficiency anaemia and pulmonary infiltrates on chest X-rays [1]. The gold standard for diagnosis is considered to be lung biopsy [2]. However, given its invasive procedure, lung biopsy is rarely used in children. The detection of hemosiderin-laden macrophages in sputum, bronchoalveolar lavage fluid (BALF) and gastric aspirates is an important means of diagnosing IPH [3]. Epidemiological reports of this disease based on large amounts of clinical data are limited. The estimated incidence ranges from 0.24 to 1.23 cases per million among children [4, 5]. A review of the French pediatric registry demonstrated that females were more susceptible to the disease [6]. To date, there are no international or national therapeutic guidelines on IPH, regarding the choice of medications, dose, and duration of therapy. The impact of the therapy on the long-term prognosis of patients with IPH has not been confirmed [7].

To date, most of the related research reports are case reports. According to the literature, the age of diagnosis lags behind the age of disease onset. A considerable proportion of IPH patients may be observed for several years under an incorrect diagnosis of treatment-resistant iron-deficiency anaemia and repeated pneumonia [6, 8]. Systematic evaluations are needed to improve timely recognition, prevent misdiagnosis and unnecessary interventions. This study aims to review the clinical characteristics, therapeutic response and outcome in a single tertiary center in China, and to discover the risk factors for recurrence in children with IPH, which will be of guiding significance for early diagnosis and reasonable treatment of the disease.

Materials and methods

Subjects and ethics statement

This study was conducted retrospectively at West China Second University Hospital, Sichuan University, a tertiary medical center in Sichuan province. Children who were diagnosed with IPH between September 2009 and November 2020 and had regular outpatient follow-up since then were enrolled in the study. Although lung biopsy was thought to be the gold standard method for the diagnosis of IPH, it was rarely used in the diagnosis of IPH in children due to its invasive procedure. IPH in children was mainly diagnosed based on clinical manifestations, imaging features, laboratory examination and exclusion of other diseases. Patients with IPH were defined as follows: (1) The child had one or more of the following symptoms: haemoptysis, dyspnoea, hypoxemia, anaemia, cough and so on; (2) Hemosiderin-laden macrophages were found in sputum / gastric fluid / alveolar lavage fluid / lung tissue biopsy; (3) Pulmonary infiltrates on chest imaging; (4) Exclusion of other diseases, which were associated with diffuse alveolar hemorrhage, such as bronchiectasis, interstitial pneumonia, neoplasms, cardiovascular disease, coagulation disorders, infections, connective tissue diseases, celiac disease, and systemic vasculitis [3, 9]. The Institutional Review Board / Ethics Committee affiliated with West China Second University Hospital, Sichuan University, approved this study (Ethics review number: 2022074), which was performed in accordance with the ethical standards of the Declaration of Helsinki.

Data collection and outcome measures

All data were retrieved by searching inpatient and outpatient electronic medical records. The data of children’s age, sex, manifestations, diagnosis, radiological characteristics, and other clinical information were collected. Short-term efficacy was assessed after 6 months of corticosteroid (CS) therapy. The improvement of clinical symptoms such as anaemia, haemoptysis, dyspnoea, fatigue, improvement of imaging lesions, recurrence rate and side effects during treatment were evaluated as outcome indicators.

Definitions

Anaemia was defined as haemoglobin (Hb) level less than 11.0 g/dl in a child aged between 6 months and 6 years old, and less than 12.0 g/dl in a child aged 6 years and older. Low-dose corticosteroid (CS) was defined as 1–2 mg/kg.d prednisolone equivalent, and the corticosteroid dose was reduced every 2–4 weeks thereafter. Sequential CS treatment was defined as 10–30 mg/kg.d methylprednisolone for 3 days followed by 1–2 mg/kg/day prednisolone. Disease recurrence was defined as exacerbation of symptoms or worsening of imaging findings after remission of clinical symptoms and imaging conditions following regular CS therapy. The allergic history of the child was defined as positive for the allergen through blood IgE levels and the presence of associated allergic manifestations (such as allergic rhinitis, allergic dermatitis, repeated wheezing, etc.).

Statistical analysis

The data were analysed using the Statistical Package for Social Sciences (SPSS), version 26.0 software (IBM, Armonk, NY). Continuous variables were compared using the Student t test or the nonparametric Mann-Whitney U test. And categorical variables were compared using the Fisher’s exact test. Two-sided P values of < 0.05 were considered statistically significant.

Results

A total of 32 patients who had regular visits in the outpatient department after diagnosis were included in this study and the longest follow-up period was 5 years. Pulmonary hemosiderin cells were found in the alveolar lavage fluid of 21 patients, in the gastric fluid of 6 patients, and in the sputum of 5 patients. To rule out other causes of haemoptysis, various tests were performed, including immunological tests (cellular immunity, humoral immunity, autoantibodies, antineutrophil cytoplasmic antibodies, and anticardiolipin antibodies), echocardiography, etiological examinations (sputum / alveolar lavage fluid bacterial culture, alveolar lavage fluid fungal culture, alveolar lavage fluid X-pert, T-SPOT, nucleic acid test of mycoplasma pneumoniae and chlamydia, fungal G and GM tests), chest enhanced CT, and coagulation function. None of the children in this study had abnormal results on the above tests.

The onset ages of these children ranged from 7 months to 12 years. The male-to-female ratio was 7:25. The mean gap between the onset of symptoms and diagnosis was 5 (0.25-36) months. Eight (8/32, 25%) children had an allergic history. The haemoglobin (Hb) levels at initial diagnosis ranged from 29 g/L to 92 g/L, indicating mainly moderate (43.8%) to severe (43.8%) anaemia. Positive immunological markers (ANA) were found in 2 (6.3%) patients. According to the imaging studies, 26 (26/32, 81.3%) children exhibited ground-glass opacity (Table 1; Fig. 1). Regarding the symptoms at initial diagnosis (Table 2, 3), 18 (18/32, 56.3%) children had haemoptysis, 24 (24/32, 75%) patients had cough, and 16 (16/32, 50%) children had fever, 6 (6/32, 18.8%) children had dyspnoea, 5 (5/32, 15.6%) children had fatigue, and 2 (2/32, 6.3%) children had wheezing, and 29 (29/32, 90.6%) children had anaemia. There were 2 and 3 patients without hemoptysis and fatigue symptoms at the beginning of the disease respectively, but symptoms gradually appeared with the progression of the disease.

Table 1 Demographic and clinical characteristics of the pediatric patients with IPH (n = 32)

Variables	N(% or range)	
Age at onset (months)	48 (7-153)	
Duration between onset and diagnosis (months)	5 (0.25-36)	
Male	7 (21.9)	
Premature newborns	3 (9.4)	
Recurrent respiratory infection	1 (3.1)	
Allergic history	8 (25)	
Egg allergy	5 (15.6)	
Milk allergy	7 (21.9)	
Dust mites allergy	3 (9.4)	
Antibiotic allergy	2 (6.3)	
Hb levels of initial diagnosis	61 (29–92)	
Severity of anaemia at initial diagnosis		
Hb 90–110 (120) g/L	1 (3.1)	
Hb 60–90 g/L	14 (43.8)	
Hb 30–60 g/L	12 (37.5)	
Hb<30 g/L	2 (6.3)	
Positive ANA	2 (6.3)	
Chest imaging		
Ground-glass opacity	26 (81.3)	
Nodular changes	8 (25.0)	
Patchy density	9 (28.1)	
Interstitial changes	4 (12.5)	
Consolidation	4 (12.5)	
Tractive bronchiectasis	2 (6.3)	
Hb: haemoglobin. Interstitial changes included thread net, interlobular septal thickening, and strip shadows on the image of lung. ANA: antinuclear antibody

Table 2 Treatment plan and short-term efficacy of IPH treatment after 6 months of CS therapy (n = 32)

Variables	N (%)	
Treatment plan		
Low-dose CS (1-2 mg/kg.d)	21 (65.6)	
High dose CS (10-20 mg/kg.d) followed by low-dose CS	5 (15.6)	
High dose CS (20-30 mg/kg.d) followed by low-dose CS	3 (9.4)	
Low-dose CS + immunosuppressant	3 (9.4)	
Duration between CS and immunosuppressant use		
1-2months	1 (3.1)	
6-12months	2 (6.3)	
Healed or improved	31 (96.9)	
Anaemia	29 (90.6)	
Healed	17 (53.1)	
Improved	11 (34.4)	
Ineffective	1 (3.1)	
Haemoptysis	18 (56.2)	
Healed	10 (31.2)	
Improved	7 (21.9)	
Ineffective	1 (3.1)	
Dyspnoea	6 (18.8)	
Healed	5 (15.6)	
Improved	1 (3.1)	
Fatigue	5 (15.6)	
Healed	3 (9.3)	
Improved	2 (6.3)	
Imaging examination	21 (65.6)	
Healed	6 (18.8)	
Improved	14 (43.7)	
Ineffective	1 (3.1)	
Adverse effect	7 (21.9)	
Respiratory tract infections	4 (12.5)	
Cushing appearance	2 (6.3)	
Vitamin D deficiency	1 (3.1)	
CS: corticosteroids

Fig. 1 Computed chest tomography of IPH. a. Chest CT showing ground-glass opacity; b. Chest CT showing patchy density and bronchiectasis (red arrow); c. Chest CT showing mass-like high-density shadows

There were 21 (21/32, 65.6%) patients who received low-dose CS, 8 (8/32, 25%) patients who received sequential CS treatment, and 3 (3/32, 9.4%) patients who were treated with low-dose CS plus an additional immunosuppressant (HCQ, hydroxychloroquine). The indications for sequential CS treatment consisted of tachypnea and dyspnea (3/8, 37.5%), severe anemia (2/8, 25%), and signs of active pulmonary hemorrhage (haemoglobin decreased progressively and chest CT showed ground-glass opacity or cloudy shadows) (3/8, 37.5%). Adverse effects of the above treatment were found in 7 (7/32, 21.9%) cases, which included respiratory tract infections (4/7, 57.1%), a cushing appearance (2/7, 28.6%) and vitamin D deficiency (1/7, 14.3%) (Table 2). In addition, 5 (5/32, 15.6%) patients received mechanical ventilation during the disease course (Table 3).

Table 3 Comparison of clinical characteristics and therapeutic effects between the low-dose CS and sequential CS treatment groups during short - term follow-up (n = 32)

Variables	Low-dose CS
(n = 24)	Sequential CS treatment (n = 8)	P	
Age of onset (months) a	48 (13–146)	37 (7-153)	0.585	
Duration between onset and

diagnosis (months) b

	4.63(0.25-36)	2 (0.25–5.25)	0.121	
Male	5 (20.8)	2 (25)	1	
Symptoms of initial diagnosis				
Haemoptysis	13 (54.2)	5 (62.5)	1	
Cough	17 (70.8)	7 (87.5)	0.642	
Fever	14 (58.3)	2 (25)	0.220	
Dyspnoea	5 (20.8)	1 (12.5)	1	
Fatigue	3 (12.5)	2 (25)	0.578	
Wheezing	2 (8.3)	0	1	
Severe anaemia	10 (41.7)	4 (50)	0.703	
Hb levels of initial diagnosis (g/L) c	61.09 (29–92)	54 (39–82)	0.608	
The lowest level of Hb (g/L) d	57.96 (29–89)	53 (39–58)	0.519	
Mechanical ventilation during the disease course	4 (16.7)	1 (12.5)	1	
Relapse	15 (62.5)	4 (50)	0.684	
Healed or improved	23 (95.8)	8 (100)	1	
Adverse effect	5 (20.8)	2 (25)	1	
Data of a, b, d, e were compared using Mann-Whitney U test. Other data in this table were compared using Fisher’s exact test

Short-term efficacy was evaluated after 6 months of CS therapy (Table 2). Among the 32 follow-up patients, 31 (31/32, 96.9%) patients were cured or improved, which was defined as complete or partial remission of symptoms or imaging findings. Twenty-nine (29/32, 90.6%) patients had symptom of anaemia at the initial diagnosis of the disease, of whom 17 (17/29, 58.6%) were cured. There were 18 (18/32, 56.2%) children with hemoptysis symptoms, and 10 (10/18, 55.5%) of the children were cured. Six (6/32, 18.8%) of the children had symptoms of dyspnoea, and 5 (5/6, 83.3%) of the children were cured. Five (5/32, 15.6%) of the children had symptoms of fatigue, and 3 (3/5, 60%) of them were cured. Twenty-one (21/32, 65.6%) patients underwent imaging examination again after 6 months of therapy, and 6 (6/21, 28.6%) of them had complete absorption of the lung lesions. One patient expired during the follow-up because of uncontrollable pulmonary bleeding.

We then compared the clinical characteristics and short-term therapeutic efficacy of low-dose CS and sequential CS treatment groups during follow-up (Table 3). We found that there were no significant differences between the two groups in the clinical features (including age of onset, sex, symptoms, Hb levels, and mechanical ventilation), as well as therapeutic effects and adverse effect. After treatment with a full dose of CS therapy, most children achieved remission (complete and partial remission) when we assessed the treatment efficacy (at the 6 months after CS therapy), but 19 of the children experienced a relapse. The causes of disease recurrence included infection (37.5%), glucocorticoid reduction (18.8%), and irregular medication (6.3%). There were 6 patients with multiple relapse factors.

In order to explore the risk factors for disease relapse, we analysed the clinical characteristics of children with or without disease relapse. No significant differences were found between those two groups as for sex, age of onset, duration between onset and diagnosis, symptoms at initial diagnosis, Hb levels, and mechanical ventilation. However, the number of children with a history of allergy in the recurrent group was significantly greater than that in the relapse-free group (p = 0.01) (Table 4). Cox regression analysis showed that allergic history was an independent factor associated with the disease recurrence. The risk of disease recurrence in children with a history of allergy was 4.255 (HR 4.255, 1.107–16.356) times higher than that in children without a history of allergy.(Table 5).

Table 4 Analysis of clinical factors related to disease relapse

Variables	Relapse-free group
(n = 13)	Recurrent group
(n = 19)	P	
Age of onset (months) a	39 (7-136)	48 (11–153)	0.774	
Duration between onset and diagnosis (months) b	2 (0.25-24)	5.25 (0.25-36)	0.087	
Male	5 (38.5)	2 (10.5)	0.091	
Symptoms of initial diagnosis				
Haemoptysis	8 (61.5)	10 (52.6)	0.725	
Cough	11 (84.6)	13 (68.4)	0.420	
Fever	7 (53.8)	9 (47.4)	1	
Dyspnoea	3 (23.1)	3 (15.8)	0.666	
Fatigue	2 (15.4)	3 (15.8)	1	
wheezing	0 (0)	2 (10.5)	0.502	
Severe anaemia	7 (53.8)	7 (36.8)	0.473	
Hb levels of initial diagnosis (g/L) c	52 (33–86)	65 (29–92)	0.368	
The lowest level of Hb (g/L) d	49 (33–86)	57 (29–89)	0.652	
Mechanical ventilation	1 (7.7)	4 (21.1)	0.382	
Allergic history	0 (0)	8 (42.1)	0.01*	
History of high-dose CS impluse therapy	4 (30.8)	4 (21.1)	0.684	
Data of a, b, c, d were compared using Mann-Whitney U test. Other Data in this table were compared using Fisher’s exact test

Table 5 Cox regression analysis of factors associated with recurrence of IPH

Variables	HR (95% CI)	P	
Male	0.612 (0.068–5.538)	0.662	
Allergic history	4.255 (1.107–16.356)	0.035*	

Discussion

Since IPH is rare, it is poorly characterized. The lack of understanding leads to missed diagnoses and inappropriate interventions. In this study, we present a large case series of pediatric patients with IPH and provide a picture of their clinical characteristics.

The etiology of IPH remains controversial. To date, there are four main etiological theories described in the literature: the allergic, the environmental, the genetic, and autoimmune theory. The allergic theory is based on the association with “milk protein allergy” in some patients with IPH named Heiner syndrome [10]. However, no prospective study that has validated this association. According to the “environmental hypothesis”, exposure to secondhand smoking and highly potent fungal toxins from Stachybotrys chartarum was responsible for pulmonary hemorrhage, especially in children. Stachybotrys chartarum produces satratoxins that causes impaired synthesis of Collagen IV, which provides connective tissue scaffolding for the endothelial basement membrane at the alveolar-capillary junction. When inhaled at high concentrations, it disrupts angiogenesis resulting in capillary fragility and pulmonary hemorrhage [11]. Exposure to pesticides has also been cited as an association [12]. IPH has also been reported among genetically related family members. In addition, Down syndrome has been identified as a risk factor for IPH, and is possibly associated with the development of pulmonary hypertension and worse outcomes [13, 14]. However, no specific genetic abnormalities have been recognized to date. With the better understanding of the autoimmunity and clinical success in IPH patients treated with anti-inflammatory therapy, the autoimmune theory appears to be the most promising hypothesis [6, 7, 15]. There have been reported that some patients with biopsy proven IPH develop ANCA positive vasculitis many years after the initial diagnosis of IPH [16]. However, several pathological studies found within earlier reports of IPH also refuted the association with autoimmune diseases [17–19]. Although there is no guidance for treatment, systemic CS therapy is considered to be the first line treatment for IPH [20]. In addition, immunosuppressive agents, mainly azathioprine (AZA), hydroxychloroquine(HCQ) and cyclophosphamide, have been proposed for patients with unfavourable response to CS [8, 21, 22]. HCQ was the most frequently used non-CS medication for remission of IPH induction treatment during an acute episode [23].The combination of CS and AZA was reported to be the most efficacious regimen for preventing recurrent disease [20].

In our study, the symptoms of all patients were generally nonspecific and included cough, wheezing, dyspnoea, haemoptysis, fever, anaemia and fatigue, which were very common in children with respiratory infections. Anaemia (mainly moderate and severe anaemia) and cough were the most common symptoms, but the typical triad was less common. In our study, the mean gap between the onset of symptoms and diagnosis was 5 (0.25-36) months, which revealed an obvious delay in diagnosis. This delay in diagnosis may be due to the atypical and nonspecific clinical manifestations and lack of awareness about the disorder. Most of the children in this study had diffuse ground-glass opacities on chest imaging. Patients with a history of recurrent lower respiratory tract infection and treatment-resistant anaemia should be examined for IPH. Chest radiography is a good and noninvasive choice for further examination even in the absence of pulmonary symptoms. In addition, 6.3% of the children had positive immunological tests, and 25% had a history of allergy, which suggested that the disease might be related to the mechanism of allergy and immunity.

All follow-up patients were initially treated with CS, and three patients received HCQ plus low-dose CS therapy during follow-up. The possible preference of HCQ over AZA is likely due to the safety profile of HCQ. Most patients received low-dose CS therapy and achieved clinical cure or partial remission after 6 months of regular treatment. Specifically, most of the clinical symptoms can be completely relieved, while most of the imaging changes can be only partially relieved. This may be related to the insufficient follow-up time. However, it also reveals that clinical remission occurs much earlier than imaging remission in children with IPH. Some previous studies reported that the Hb concentration might be one of the key markers for monitoring the response to treatments, and helping to adjust medication. A longer duration of Hb recovery was associated with the need for additional CS treatments [1]. In our study, 90.6% of the follow-up patients had a symptom of anaemia, and the improvement in anaemia after treatment was consistent with the overall improvement in disease severity, which further verified the important role of Hb in treatment response.

During the follow-up, we found that the recurrence rate of this disease was high, and respiratory tract infection was the most common factor that induced the recurrence of this disease. Moreover, respiratory infection was the most common adverse effect of CS therapy. Therefore, effective prevention and treatment of respiratory tract infection are common challenges for both doctors and patients, and also will be an important means for reducing disease recurrence.

Cheng-Tsung Yang reported that high dose CS was associated with decreased ICU admission risk and that high-dose CS treatment promoted Hb recovery even in more severe cases [1]. In our study, we compared the clinical characteristics between the low-dose CS group and sequential CS treatment group, and found no statistically significant difference in clinical features between the two groups. Then, the therapeutic effects on children in the low-dose CS group and sequential CS treatment group were compared, and no significant difference was found as well. This reveals that although children in the sequential treatment group had more severe clinical symptoms and pulmonary hemorrhage compared to those in the low-dose CS group, the prognosis of this disease in these patients after sequential treatment was comparable to that in the low-dose CS group. However, a history of high-dose CS impluse therapy did not reduce the recurrence rate of the disease. This will be instructive for our clinical treatment selection.

Interestingly, we found that the number of children with a history of allergy in the recurrent group was significantly greater than that in the nonrecurrent group. Cox regression analysis showed that children with a history of allergy tended to experience recurrence (HR 4.255, 1.107–16.356), which suggested that the occurrence and development of the disease may be closely related to allergy. This finding is consistent with the allergic hypothesis of the disease.

There were several potential limitations of our study. Firstly, because of the retrospective design, selection and observational bias may have affected the results. Secondly, it was a single-center study with a moderate sample size, which may not be generalizable. Thirdly, only 9 children were followed up for more than 3 years in this study, which limited our analysis of the long-term efficacy and prognosis of this disease. A more prolonged, match-controlled study to evaluate different immunosuppressive regimens will be valuable, but it is also difficult to perform given the rarity of the disease. In addition, cohort studies are needed to further explore the relationship between IPH and autoimmune diseases.

Summary and conclusions

Anaemia and cough are the most common symptoms in children with IPH, but the typical triad is less common. There is an obvious delay in diagnosis of this disease. The disease is prone to relapse. Respiratory tract infection is the most common factor to induce the recurrence of this disease. Children with allergic history tend to experience disease recurrence. Low-dose CS therapy is effective and safe. Most patients can achieve clinical cure or partial remission after treatment. Radiographic remission lags behind clinical remission. Even if the child’s disease is severe, a good long-term prognosis can be obtained after high-dose CS impluse therapy. However, a history of high-dose CS impulse therapy cannot reduce the recurrence rate of the disease.

Acknowledgements

The authors thank all the colleagues in the management team at Division of Pediatric Pulmonology and Immunology, West China Second University Hospital, Sichuan University. The authors thank all the participating patients.

Author contributions

LW collected and analyzed all the clinical data, drafted and revised the manuscript. HL and LC designed and revised the manuscript. YL and RZ collected the clinical data. All the authors have reviewed and approved the final manuscript.

Funding

This study was supported by the following funding: (1) General Program of National Natural Science Foundation of China (82370001); (2) Major Scientific and Technological Project from Science &Technology Department of Sichuan Province (2022ZDZX0021); (3) Fundamental Research Funds for the Central Universities (SCU2022D022); (4) Development Fund for Clinical Discipline of West China Second Hospital of Sichuan University (KL118).

Data availability

All the datasets generated and analysed in the present study are included in this published article.

Declarations

Ethics approval and consent to participate

The Institutional Review Board/Ethics Committee affiliated with West China Second University Hospital, Sichuan University, approved this study (Ethics review number: 2022074), which was performed in accordance with the ethical standards of the Declaration of Helsinki. This was a retrospective study, and the data were anonymous. The requirement for informed consent was therefore waived.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Abbreviations

IPH Idiopathic pulmonary hemosiderosis

CS Corticosteroid

ANCA Antineutrophil cytoplasmic antibody

Hb Hemoglobin

HCQ Hydroxychloroquine

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