Coughed Up Old Phlegm and Got Sick Again

• Journal List
• J Thorac Dis
• v.8(12); 2022 Dec
• PMC5227256

J Thorac Dis. 2022 December; 8(12): 3468–3477.

A 43-year-old human being with cough, expectoration and recurrent wheezing

Hongyu Wang,^{1, 2, *} Ruchong Chen,^{1, *} Jiaxing Xie,^{ane, *} Qingling Zhang,^{i, *} Yu Deng,^{1, *} Qingsi Zeng,^{1, *} Zheng Zhu,^{1, *} Ming Ding,^{i, *} Zhengdao Lai,^{1, *} Martin Kolb,^{2, *} Paul O'Byrne, ^{two, *} Rongchang Chen,^{i, *} and Nanshan Zhong ^{1, *}

Hongyu Wang

¹State Key Laboratory of Respiratory Illness, National Clinical Inquiry Heart for Respiratory Disease, Guangzhou Institute of Respiratory Disease, Offset Affiliated Infirmary of Guangzhou Medical Academy, Guangzhou 510120, Mainland china;

²Firestone Institute for Respiratory Health, The Research Establish of St. Joe's Hamilton, St. Joseph's Healthcare; Department of Medicine, McMaster University, Hamilton, Canada

Ruchong Chen

¹State Key Laboratory of Respiratory Disease, National Clinical Inquiry Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, People's republic of china;

Jiaxing Xie

¹Country Primal Laboratory of Respiratory Disease, National Clinical Enquiry Center for Respiratory Affliction, Guangzhou Institute of Respiratory Disease, Get-go Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China;

Qingling Zhang

¹State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Constitute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China;

Yu Deng

^oneCountry Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Affliction, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China;

Qingsi Zeng

¹Land Fundamental Laboratory of Respiratory Illness, National Clinical Research Middle for Respiratory Disease, Guangzhou Institute of Respiratory Disease, Get-go Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China;

Zheng Zhu

^oneLand Key Laboratory of Respiratory Affliction, National Clinical Enquiry Center for Respiratory Illness, Guangzhou Institute of Respiratory Disease, First Affiliated Infirmary of Guangzhou Medical University, Guangzhou 510120, China;

Ming Ding

¹Land Cardinal Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Affliction, Guangzhou Found of Respiratory Affliction, First Affiliated Infirmary of Guangzhou Medical Academy, Guangzhou 510120, China;

Zhengdao Lai

¹State Cardinal Laboratory of Respiratory Affliction, National Clinical Enquiry Center for Respiratory Affliction, Guangzhou Institute of Respiratory Affliction, Start Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China;

Martin Kolb

ⁱⁱFirestone Found for Respiratory Health, The Inquiry Institute of St. Joe'southward Hamilton, St. Joseph'due south Healthcare; Department of Medicine, McMaster University, Hamilton, Canada

Paul O'Byrne

²Firestone Institute for Respiratory Wellness, The Inquiry Institute of St. Joe's Hamilton, St. Joseph'south Healthcare; Department of Medicine, McMaster University, Hamilton, Canada

Rongchang Chen

¹State Primal Laboratory of Respiratory Illness, National Clinical Inquiry Middle for Respiratory Affliction, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China;

Nanshan Zhong

ⁱState Key Laboratory of Respiratory Illness, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, Beginning Affiliated Hospital of Guangzhou Medical Academy, Guangzhou 510120, China;

Case presentation

A 43-year-old homo was admitted to the Guangzhou Institute of Respiratory Disease (GIRD), the Get-go Affiliated Infirmary of Guangzhou Medical Academy because of recurrent episodes of coughing, expectoration and wheezing for iii years with aggravation during the previous vi months.

The patient began to cough with white phlegm after a cold in 2012. The cough was worse upon waking in the morning and laying downwardly at night. He had no chills, fever, chest pain, breast tightness, palpitations, night sweats, hemoptysis or paroxysmal nocturnal dyspnea. He was diagnosed with 'upper respiratory infection' in a local infirmary and received symptomatic treatment for several days that he could non recall clearly. His condition improved, but he still had occasional relapses. One month after the treatment, he suffered from an attack of wheezing during moderate activity and was admitted to a local hospital, in which he was diagnosed with 'bronchial asthma' and 'type 2 respiratory failure', from 1st December to 13th Dec 2012. Chest CT browse showed interstitial inflammation in the right middle and left upper lobe. Pulmonary part test suggested balmy obstructive ventilatory dysfunction with FEV₁ at 72.2% of predicted, FVC at 89.7% of predicted, and FEV₁/FVC ratio at 66.81%. The bronchodilator reversibility exam was positive: FEV_one increased >12% and >200 mL with inhaled Ventolin 400 µg ( Figure 1 ). No abnormalities were noted in echocardiogram. Inflammation was observed in both bronchial trees on bronchoscopy. Later on receiving symptomatic treatment, the patient'south status improved but did non normalize. Upon referral, he was admitted to our hospital for further treatment. The treatment included Methylprednisolone at a daily dose of 40 mg intravenously and oral Theophylline 0.2 g once every 12 hours for iii days. After that, his condition improved and he was subsequently discharged. He continued to take Singulair, Ketotifen and Theophylline, as well as Symbicort 320/nine µg bid and Foster 100/6 µg bid. His symptoms were under command.

Pulmonary role test (performed on Dec 25th, 2012 and May 26th, 2015, respectively).

The patient was re-admitted on May 25, 2015, six months before which, his symptoms recurred and were worse in cold weather condition. He began to wheeze after balmy activity and coughed with increasing white phlegm. He received intravenous handling with unknown regimen in a local hospital for a couple of days, but his status was non improved. So he was referred to our hospital for further treatment. Since the onset of the disease, his appetite stayed the aforementioned with normal stool and urine. He lost 6 kilograms in six months.

He had no known allergies, but he had been suffering from cataract for nearly 1 year, gallbladder polyps and fatty liver for well-nigh 4 years. He was non exposed to an epidemic surface area before admission. He had smoked for ten years, which was about 5 pack years, and ceased smoking 10 years agone. He got married at 25 and got forth with his wife well. He had 1 son and i daughter, both of whom were healthy. No relevant family history was identified and no one in his family had similar symptoms.

On access, vital signs were stable. The temperature was 36.8 °C, the pulse was ninety beats per minute and regular, the blood pressure was 120/73 mmHg and the respiratory rate was xx breaths per minute. He was well developed and moderately nourished and free from skin eruption. Multiple flaky red macules, about 2 to 4 centimeters in bore, were noted on both lower extremities without pruritus. He felt mild pain when pressing the red macules. There was no spider angioma. Superficial lymph nodes were not enlarged. The respiratory movement was bilaterally symmetric. Breath sounds from both lungs were coarse and wheezes were heard during expiration. Middle sounds and the remainder of physical examination were normal. His annual lab examination in May 2022 showed elevated serum full IgE (1,072 kU/L) and high percent of eosinophils in peripheral blood (27.8%). Fractional exhaled nitric oxide (FeNO) was 37 ppb. The proportions of induced sputum cell counts were as follows: neutrophils 62.5%, macrophages 31%, eosinophils 2% and lymphocytes four.v%. In bronchoalveolar lavage fluid (BALF), the proportions of cells were as follows: neutrophils 53.5%, macrophages x.v%, eosinophils 35% and lymphocytes 1%. Eosinophils in peripheral blood were normal, although os marrow puncture showed active eosinophil hyperplasia when he received treatment in our hospital for 3 days. Sputum smear tests for fungi and TB were all negative for 4 times. Fungal sputum culture and antigen examination were too negative. The results were negative for mycoplasma pneumonia and HIV. Other test results are shown in Table 1 .

Table 1

Laboratory data

Variables	Reference ranges	May 26, 2015	Jun five, 2015	On current admission (Jul 20, 2015)
Completed blood count (CBC)
White blood jail cell (WBC) (×10nine/L)	4.0–10.0	9.68	14.five	12.73
Neutrophils (N)	forty.0–70.0	36.3	66.1	threescore.8
Eosinophils (Eastward)	0.0–vii.0	27.8	0	0.4
Lymphocytes (L)	10.0–50.0			30.7
Monocytes (Thou)	3.4–nine.0			7.6
Basophils (B)	0.0–i.5			0.five
Live function exam (LFT)
Total poly peptide (TP) (thou/L)	65–85			56.2
Serum full bilirubin (STB) (ìmol/L)	1.seven–22.2			two.5
HDL-C (mmol/L)	i.17–two.00			1.59
TG (mmol/L)	0.23–1.58			2.54
Hepatitis B exam (HBV-test)
Anti-HBs (mIU/mL)	<x.00			10.99
Anti-HBc (s/co)	<1.00			2.53
MI test
CK-MB (U/50)	3–25			xiv.0
LDH (U/Fifty)	109–255			223.4
Troponin I (TnI) (ug/L)	0–0.04			0.01
Coagulation exam
Fibrinogen (Fg) (thousand/50)	4.3			ii.79
D-Dimer (ng/mL)	565			342
Claret gas test
PO2 (mmHg)	83.0–108.0			77.7
PCOii (mmHg)	35.0–48.0			44.five
PH	7.350–7.450			seven.428
HCO3 − (mmol/L)	21.4–27.3			28.9
SB (mmol/L)	−2.3 to 3.0	−3.three		4.vii
ESR (mm/h)	0–xx	25		seven
Pct (ng/mL)	<0.05	<0.05
ANCA
PR3 (U/mL)	0–18	2.06	2.14	0.17
MPO (U/mL)	0–xviii	eight.58	9.21	5.57

CBC, complete blood count; WBC, white-cell count; STB, serum full bilirubin; HDL-C, high-density lipoprotein cholesterol; TG, triglyceride; Anti-HBs, hepatitis B surface antibody; Anti-HBc, hepatitis B core antibody; MI, myocardial infarction; CK-MB, creatine kinase-MB; LDH, lactate dehydrogenase; Fg, fibrinogen; PTT, partial thromboplastin time; ESR, erythrocyte sedimentation charge per unit; PCT, procalcitonin examination; ANCA, anti-neutrophil cytoplasmic antibodies; PR3, protease proteinase-3; MPO, myeloperoxidase.

Since admission to our hospital, nebulized compound ipratropium bromide solution ii.5 mL every 8 hours and budesonide two mL every 12 hours had been administered. The patient's condition was not improved. On June 8th in the hospital, the patient was treated with intravenous cyclophosphamide (CTX) 0.2 g every other twenty-four hour period for 3 days, and then with oral CTX as subsequent therapy ( Table 2 ) for three days, after which, his symptoms of wheezing and cough improved.

Tabular array ii

Patient handling with systemic corticosteroids and immunosuppressive agents

	Methylprednisolone (intravenous drip, daily) (mg)	Prednisone (orally, daily) (mg)	Cyclophosphamide (intravenous drip, every other day) (mg)	Cyclophosphamide (orally, twice a twenty-four hour period) (mg)
May 27–May 31	40	–	–	–
Jun one–Jun 4	80	–	–	–
Jun 4–Jun 7	160	–	–	–
Jun eight–Jun ten	–	–	200	–
Jun 11–Jun eleven	–	–	–	–
Jun xi–Jun 12	lxxx	–	–	–
Jun 12–Jun 25 (on discharge)	–	lx	–	50
Jun 25–Jul 9	–	55	–	50
Jul 9–	–	40	–	50

On the second twenty-four hours in the infirmary, chest CT scans revealed signs of bronchiolitis obliterans on bilateral lungs and nodules were noted in the right lower lobe ( Figure 2 ). Pulmonary function test suggested astringent obstructive ventilatory dysfunction with FEV₁ at 34.70% of predicted, FVC at 73.4% of predicted, and FEV₁/FVC ratio at 38.58%. The bronchodilator reversibility test was positive: FEV₁ increased >12% and >200 mL with inhaled Ventolin 400 µg. Diffusion capacity declined mildly and airway resistance was normal ( Figure 1 ).

CT scans of the breast (console C, Eastward performed on March 27th, 2013; panel D, F performed on May 26th, 2015) and sinus (panel A performed on Apr 11th, 2013, panel B performed on May 26th, 2015).

In turbinate mucosal tissue, basement membrane thickening, mucosal edema, scattered lymphocytes and few eosinophils was noted. Likewise, the patient presented with focal epithelial squamous metaplasia, local thickening of basement membrane, submucosal edema, polish muscle hyperplasia, increased lymphocytes and eosinophils on the mucous membrane of the lower right bronchus. Bronchiole wall was thickened on the right lower lobe, fibrous hyperplasia was noted, cellulose effused in alveolar cavities, focal lymphocytic infiltration was observed, bronchial wall and pulmonary interstitial presented with more eosinophil infiltration without vasculitis and granuloma.

Why is a grand circular discussion warranted for this patient?

Dr. Qingling Zhang (Pulmonologist at GIRD):

After the treatment with a big dose of steroids and CTX for three days, the patient felt much better with no wheezing and only a bit of cough. The dose of CTX was reduced from 200 mg with intravenous baste every other day to 50 mg orally twice a day. With treatment, the patient'southward condition further improved and the symptoms were relieved and his blood eosinophils count decreased. CT scans of chest and sinus showed milder inflammation in both lungs and sinus than before. In terms of lung part, spirometry on June 11 later on loftier dose steroids treatment suggested mild obstructive ventilatory dysfunction, which was much better than his condition on admission in May earlier the steroids and CTX treatment. FEV₁ increased to 77% of predicted. This patient was discharged on the 12th mean solar day (July 12). Then he was followed up in clinic, the systemic corticosteroid was gradually stepped downwards from a daily dose of prednisone 60 to forty mg in 4 weeks and maintain CTX fifty mg orally twice a mean solar day. Recently, we re-examined his lung role. His spirometry results were a flake worse than the previous one in June and suggested moderate obstructive ventilatory dysfunction with FEV_one 66% of predicted. Tiptop flow monitoring indicated that the values been improved profoundly since June 8th when we started high dose steroids as well as CTX, and the values had been stable in the post-obit outpatient clinic until now. This patient met four items of the diagnostic criteria of Eosinophilic Granulomatosis with Polyangiitis [EGPA, formerly known equally Churg-Strauss syndrome (CSS)], including asthma, peripheral claret eosinophils greater than 10%, abnormalities in the paranasal sinus, and non-fixed pulmonary infiltrates. We were because this patient might exist with EGPA, which only affected the lung. Therefore, the purposes of today'due south discussion are as follows: (I) could this patient exist diagnosed with EGPA or chronic eosinophilic pneumonia (CEP)? Or has he suffered from a special phenotype of severe asthma? (Two) how to foreclose the side effects from using loftier dose steroids and CTX? (III) how to manage his farther treatment including the steroids and immunosuppressive agent, as well every bit the side effects?

Prof. Nanshan Zhong (Grand round moderator, Pulmonologist at GIRD):

This case raised two questions. Beginning, whether the patient could be diagnosed with EGPA, or merely be diagnosed with very severe asthma (refractory asthma), or some other diseases similar CEP? Secondly, how to manage the relatively big dose of corticosteroids and related side effects?

Before the discussion, we shall provide breast imaging data and pathologic data. Showtime of all, I would like to invite Dr. Zeng to nowadays the radiological information.

Images and pathological discussion

Dr. Qingsi Zeng (Radiologist at GIRD):

The starting time CT scan was performed in March 2013. It showed decreased attenuation of both lungs, air trapping, and lengthened thickening of bronchial walls. The second chest CT browse performed vii months afterwards (October 2013) revealed comeback of the thickening of bronchial wall and the recoiled pattern disappeared after treatment. The lesions included centrilobular nodules, tree-in-bud sign in the upper and lower lobe and the thickening of bronchial walls showed on May 2022 were more remarkable than that in 2013 ( Effigy two ). The CT findings indicated the disease was progressing. But the latest CT browse after two months of treatment (July 2015) showed the infiltration disappeared and both lungs were clear. Information technology's confusing that the thickening of the bronchial wall still recurred this year even after effective treatment and improvement this calendar month (July 2015). The dynamic CT series (July 2015) suggested the patient was recovering. All these findings point small airway diseases, generally like a kind of untypical severe asthma. The sinus CT scan showed inflammation of bilateral maxillary sinus and ethmoidal sinus.

Prof. Nanshan Zhong:

Autonomously from the changes of bronchus, whether the patient had pneumonia when his symptoms recurred is extremely of import for the states to brand diagnosis, for example, CEP or others, even CSS. May I inquire Dr. Zeng, do yous think this patient had pneumonia from the radiological point of view?

Dr. Qingsi Zeng:

We don't recollect this patient had pneumonia because nosotros cannot see whatever basis-glass opacity or consolidations. We just saw very tiny lesions with small centrilobular nodules and tree-in-bud. All evidence from CT scans is related to airway diseases.

Prof. Nanshan Zhong:

Are there any split or tiny signs of pneumonia?

Dr. Qingsi Zeng:

No, nosotros don't call back so.

Prof. Nanshan Zhong:

OK. This is very important for united states of america to think nearly the diagnosis. Permit'south move to the pathological information session. I would like to invite Dr. Gu to introduce the histological data.

Dr. Yingying Gu (Pathologist at GIRD):

Biopsies of the nasal mucosa, mucosa membrane of bronchus and lung were conducted on this patient. Let me innovate the biopsy of the nasal mucosa showtime. Sample of the nasal mucosa was obtained, covered by pseudostratified columnar ciliated epithelium predominantly. Widening of basement membrane was noted. Edema was seen under the mucosa and it looked pale. Scattering lymphocyte and a few eosinophils were infiltrated. A specimen of the bronchial mucosa revealed that pseudostratified columnar ciliated epithelium was predominant. Eosinophils infiltration and edema were observed under the mucosa. Another piece of the bronchial specimen also showed obvious edema on the mucosa with more than eosinophils infiltration. There were no signs of vasculitis presented on the small vessels. The slice of transbronchial lung biopsy showed a lot of eosinophils and lymphocytes infiltration in the interstitial tissue, even so, no eosinophilic angiitis was noted around the pocket-sized vascular walls. A few eosinophils exudation were constitute in the alveolar space, while more than eosinophils were infiltrated in the alveolar septum ( Figure three ). The offset diagnosis we considered was EGPA. The 2nd consideration was CEP, and the possibility of idiopathic hypereosinophilic syndrome (IHES) should be excluded. In terms of the diagnosis of EGPA for this patient, there were no typical pathological changes of angiitis and granulomatosis, simply the clinical symptoms and presentations were systemic, including chronic gastritis, rashes on the skin. From the microscopy, eosinophils infiltrations were noted in nasal mucosa, bronchus, and the lung. In the early on stage of EGPA, the pathological changes of vasculitis and granulomatosis may not be presented. Commonly, it takes several years to testify the changes of angiitis and granulomatosis with the development of the disease. Therefore, a possibility of EGPA was considered beginning, and the second differential diagnosis of CEP should be excluded. Eosinophilic infiltrations in the interstitial lung tissue may also be presented in the case of CEP, simply the changes are mostly localized in the lung, non systemic. Compared to EGPA, the severity of eosinophilic infiltration of CEP is oft milder. The third diagnosis we excluded was IHES because the clinical presentation of this patient was not supportive; meanwhile, the prison cell count of eosinophils in the peripheral blood was normal and the level of eosinophils in the bone marrow was a bit higher after the treatment.

Transbronchial biopsy of the lung. Panel A was presented by original magnification ×fifty. Panel B, C and D were presented past original magnification ×100. (Hematoxylin and eosin stain).

Overall, we tend to diagnose this case with EGPA according to the clinical presentation and pathological findings, as well as the comparison of three differential diagnoses.

Prof. Nanshan Zhong:

Dr. Gu, how practice you think about the diagnosis of astringent asthma based on the pathological findings?

Dr. Yingying Gu:

For astringent asthma, the pathological changes usually are localized in the bronchial mucosa, smoothen musculus hypertrophy accompanied with mucous gland hyperplasia should also be seen, and there are not many eosinophilic infiltrations in the lung. However, obvious eosinophilic infiltration was presented in the lung of this patient, so I adopt to a diagnosis of systemic disease.

Prof. Nanshan Zhong (in summary):

The pathologist has dissimilar opinions on the diagnosis. The radiologist'south diagnosis seems to exist severe asthma based on the imaging findings. There is no much radiological clue showing the lung parenchymal infiltration. However, the histological examination showed eosinophilic infiltration in the bronchus and the alveoli, likewise as in the lung interstitial infinite. The diagnosis of the patient is controversial.

Now, I would like to invite experts from the Firestone Institute for Respiratory Health (FIRH) to share their opinions.

Differential diagnosis

Dr. Paul O'Byrne (Pulmonologist at FIRH):

This gentleman, first of all, has had episodes of astringent, variable airway obstruction. When he has been acutely ill, his lung part has been very severely impaired. When he is well, his lung function is not normal, but not far from normal. Secondly, he has atopy. He has an elevated total IgE over 1,000 kU/mL. Yet, we are not given whatever information about what he might exist sensitized to. I of the tests that I think nosotros'd consider here would be a very simple peel prick tests which might be helpful to provide evidence of some important allergens which he is sensitized to. If possible, avoiding these allergens might assist to improve his clinical symptoms. The third component of this case is his eosinophilia. We tin can confidently exclude a diagnosis of eosinophilic pneumonia, equally the radiologist indicated that there was no testify of consolidation in the lungs with the extensive radiographic investigations. In my stance, the diagnosis of EGPA requires pathological testify of those changes. However, you lot have pathology which shows no evidence of angiitis, vasculitis or granulomatous. Therefore, at this moment, I am fairly confident that EGPA is probably not the reason why this man was so ill.

What he does have is, in my stance, severe eosinophilic asthma. The asthma is documented by variable airway obstruction and the eosinophilia was beingness shown in his claret stream and BAL fluids, although the sputum eosinophils were very borderline and probably not elevated. He did respond very well when treated with intravenous and college doses oral corticosteroids. So, the question, is whether there is anything else that could be causing the severe eosinophilia. Could this be, for instance, allergic bronchopulmonary aspergillosis (ABPA), which can cause severe eosinophilia? Nonetheless, the radiology makes that extremely unlikely. At that place are no characteristic upper lobe changes that we see with ABPA. The question becomes whether anything else can be done to establish the diagnosis. He was very thoroughly investigated, including lung tissue biopsy. The simply additional test to do at this moment would be some skin prick testing (SPT) to identify the relevant environmental allergens. The immunological testing ANCA was negative, and ESR was not markedly elevated.

Another comment is that one of the biopsies we looked at was the airway mucosal biopsy. To me, information technology looked very much similar an asthmatic airway biopsy, with a thickening of the submucosal basal membrane and a great bargain of airway smooth muscle in that biopsy, much more than we see in a normal, non-asthmatic individual.

Altogether, I would non pursue the question of him having, at to the lowest degree at this moment, whatever evidence of vasculitis.

Dr. Gerard Cox (Pulmonologist at FIRH):

I don't think EGPA is the most likely diagnosis, but if it was present, 1 might discover it in the following way.

Firstly, the skin lesion that is referred to, we heard that was acne, which might exist a side effect of prednisone possibly simply not necessarily bear witness of vasculitis. But if the patient had any rash that was unexpected, unusual and uncommon, I call up it would be a good idea to biopsy that rash and see what tissue changes are nowadays. Secondly, the pathologist made an excellent point about vasculitis presentation and the angiitis (EGPA), and why didn't take a irresolute in presentation over fourth dimension. If we run across a patient at the very kickoff of the presentation, they might not have the unabridged syndrome present. All the same, he has been sick for 3 years, which should be near long enough for nearly things to come out. Withal, it would be a good idea to recheck his ANCA levels sometime in the future. A number of our patients with CSS had a very depression level of ANCA, ordinarily just above the upper limit of normal range and they tin certainly vary up and downward.

Nosotros heard about a few other symptoms including gastritis. Evidently, if eosinophilic gastritis or eosinophilic esophagitis was present, that would brand a diagnosis of EGPA much more solid. The biopsies of the airway (olfactory organ, bronchus and lung) showing eosinophils, according to Dr. O'Byrne'south argument most all that eosinophilic inflammation, supposed to be a track for allergic asthma and allergic rhinitis. Therefore, I think nosotros accept to find the eosinophilic infiltration outside the respiratory tract. In my opinion, tummy or esophagus given the symptoms of reflux and gastritis would be a expert identify to look for eosinophilic inflammation. I heard something about center symptoms, and I wonder if he has got whatsoever evidence of vasculitis affecting his optics. In our situation, we volition enquire for a specialist to see the patient when we worry about that because nosotros don't feel confident at the bedside excluding vasculitis of various levels of his eye. That would strengthen the statement that this is a vasculitis syndrome if it was found.

Moreover, at that place were some tests washed showing a possible involvement of the middle because some of the enzymes were raised in the claret. We would echo that assessment with an ECG to look for any problems there, as well equally echocardiogram as a minimum. At the ATS meeting this spring in Denver, there was a presentation on EGPA with cardiac interest where they showed with PET scanning. They found involvement of the myocardium in their patients with EGPA more often than expected. Then if y'all want to find evidence of some other organ involved to testify and make the case for EGPA, I think the eye would be a practiced place to look at if PET scanning is available. The final, mononeuritis has such different symptoms from allergy and asthma, so if the patient has anything suggests mononeuritis syndrome, that might modify Dr. O'Byrne's opinion away from this being astringent, allergic asthma affecting all the respiratory tract.

Discussion almost direction

Dr. Paul O'Byrne:

Some other comment is in relation to his treatment since he is being treated with cyclophosphamide. Of all the medications he'southward on, cyclophosphamide is the ane I have the most concern about side furnishings. I would terminate cyclophosphamide due to the absence of pathological evidence of vasculitis. I would manage him with systemic corticosteroids. Then I think near what else may be additional useful treatment. Ane thing that might be available and could be a value is anti-IgE, omalizumab. In that location is bear witness that omalizumab can be helpful in reducing the risk of severe exacerbations in patients with severe refractory asthma. A contempo study (1) supported that this arroyo is the almost probable to work in patients who had an elevated eosinophilia at least in the airways. That is i possibility. The second effect is optimizing his inhaled medications (dose of the inhaled corticosteroids). I would certainly care for him with a combination inhaler of ICS and LABA because the patient has variable airway obstruction and inflammation, both of those are appropriate. I personally would introduce the combination budesonide/formoterol in this treatment plan because it can exist useful every bit a maintenance treatment and every bit a rescue. We did not hear nigh how much rescue medicine the patient is taking but I suspect from his history that it is probably several times a day. So if this is true, then he should get a rescue treatment containing corticosteroid, as well as a bronchodilator. We often as well consider whether using higher doses of additional ICS, such as budesonide or fluticasone given in addition to budesonide/formoterol and endeavor to optimize the inhaled medication doses.

Dr. Andrew McIvor (Pulmonologist at FIRH):

I fully agree with Dr. O'Byrne about what he said, but I would similar to brand a small comment. One thing that I noticed is that the patient was on montelukast. In that location accept been reported a black box warning about montelukast perhaps a potentiation of CSS. There are two means this syndrome may present. Sometimes, people with severe asthma are on steroids, and if montelukast is added in, they seem to get a piddling bit better. Simply when the oral steroids are dropped, then the patients seem to develop total-blown CSS. Perchance information technology wasn't related to the drug whatsoever, but it was related to alter in handling. Churg-Strauss can also nowadays in people with quite mild asthma associated with allergic rhinitis, who then go on to develop lower vasculitic symptoms and the montelukast could be added in considering it was presumed to be mild asthma. To these patients, nosotros should always look at the benefits that can occur from increasing treatment, and this is merely one thing that I think we should bring up for teaching aspect.

Dr. Gerard Cox:

Regarding to the management, I think he's already having trouble with prednisone side effects since he's mentioned having cataracts, gastritis, acne and fatty liver. And so, these are already showing that he is at chance for more than complications from steroids. Therefore we will be very interested in a drug other than prednisone to help control his disease. You accept heard near a very expert suggestion from Prof. O'Byrne nigh anti-IgE therapy. If that isn't available to you lot and if intensive inhaled therapy isn't sufficient, when we give somebody in this situation with difficult asthma, lung eosinophilia, or maybe another syndrome, we might often use methotrexate before we used cyclophosphamide, particularly for young patients. He is only 43, and we would worry most longer-term consequences of malignancy with somebody who was treated with oral cyclophosphamide for a long flow of fourth dimension. If you have to requite him a nonsteroid drug to become away from prednisone and y'all don't get biologic 1 available to you, methotrexate might be a cheap and economical manner to become in in that location.

Final summarization

Dr. Paul O'Byrne:

Putting all things together, I think this man has severe refractory asthma with eosinophilia. I would optimize his inhaled handling and would consider, at least think virtually omalizumab. When available, the patient will probably practice very well with the anti-IL5 approaches such as mepolizumab, or benralizumab, which will be available very soon.

Dr. Nanshan Zhong:

I would like to brand a summary of our discussions. Currently, the diagnosis should be considered as severe asthma rather than EGPA because there is no evidence of consolidation in the lung according to CT browse images, and no histological testify of vasculitis and eosinophilic granuloma were found from the lung biopsies. Notwithstanding, the diagnosis of EGPA cannot exist completely excluded. If eosinophilic infiltration can be found in other organs outside the lung, for example, stomach, eyes, or heart, then EGPA should exist considered and further observation is needed. For treatment, cyclophosphamide should be used cautiously and oral steroid seems problematic due to the side effects. Additional inhaled corticosteroid such every bit budesonide should be considered. Meanwhile, the patient had a very high level of IgE, so the anti-IgE therapy might be useful. The direction of allergic rhinitis should also be strengthened. Therefore, at this moment, we agree with your opinions and treat the patient following the direction of severe asthma. Xolair will be available very soon in Prc and we can try, but anti-IL5 is not available yet. We are going to follow up very carefully with this patient as well to monitor any modify of eosinophilic infiltration in other organs and modify the diagnosis accordingly.

Acknowledgements

We would similar to express our sincere gratitude to Dr. Hongyu Wang for her kind coordination on the Grand Round between GIRD and FIRH, every bit well every bit her diligent work on structuring and revising this paper. We are grateful to Dr. Qingling Zhang for providing the case, to Dr. Zheng Zhu, Dr. Ming Ding, Dr. Ruchong Chen for drafting the manuscript, to Dr. Jiaxing Xie and Dr. Zhengdao Lai for verifying the clinical case data, to Dr. Qingsi Zeng and Dr. Yu Deng for their radiological comments, to Dr. Yingying Gu for pathological comments, and to Prof. Rongchang Chen for his facilitating the organization of Ground Round, to Prof. Nanshan Zhong for his coordination during the Ground Round, to Prof. Paul O'Byrne, Prof. Gerard Cox and Prof. Andrew McIvor for their valuable comments on the case, to Prof. Martin Kolb for editing.

Notes

A telemedicine grand round communication was held betwixt the Guangzhou Institute of Respiratory Disease (GIRD), China, and the Firestone Plant for Respiratory Health (FIRH), Canada on July 22, 2022 to talk over virtually a man with recurrent episodes of coughing, expectoration and wheezing for iii years with aggravation during the previous half dozen months.

Footnotes

Conflicts of Involvement: The authors have no conflicts of interest to declare.

References

1. Hanania NA, Wenzel Due south, Rosén K, et al. Exploring the effects of omalizumab in allergic asthma: an assay of biomarkers in the EXTRA study. Am J Respir Crit Care Med 2013;187:804-11. 10.1164/rccm.201208-1414OC [PubMed] [CrossRef] [Google Scholar]

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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5227256/

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