Clinical diagnosis, treatment, and medical identification of specific pulmonary infection in naval pilots:Four case reports

INTRODUCTION

Cryptococcal pneumonia is more common in immunodeficient people; however, in recent years, the incidence of cryptococcal pneumonia has been increasing in people with normal immune function[1,2]. While it is rare to see pilots infected with cryptococcal pneumonia, this infection may lead to central nervous system infection and serious consequences. Tuberculosis has been reported in pilots at home and abroad, ranking first in the respiratory disease spectrum of hospitalized pilots in China[3]. Most lung-specific infections caused by

or

have insidious onset and prolonged course of disease. The course of diagnosis and treatment takes more than 6 mo, and serious complications may occur that may threaten the physical and mental health of pilots. This may lead to grounding, which is a serious threat to the combat effectiveness of naval aviation corps. Therefore, it is necessary to carry out targeted research on it.

From January 2020 to November 2021, four naval pilots with specific pulmonary infection were successfully diagnosed and treated in the Aviation Disease Department of PLA Naval Medical Center, including three cases of tuberculosis and one of cryptococcal pneumonia. Three cases successfully obtained medical waiver for flight after being cured, and one was grounded after reaching the maximum flight life. The clinical data were summarized and analyzed to explore the preventive countermeasures of specific pneumonia in naval pilots.

CASE PRESENTATION

Chief complaints

A male fighter pilot, age 33 years, had multiple lumps and shadows in his left lung found by physical examination for 1 d.

A male helicopter pilot, age 30 years, had multiple patchy and nodular shadows in the left upper lung found by physical examination for 4 d.

最后，基于相對貼近度值，可以獲得各個測評對象的排序值。基于排序值，可以分析測評對象之間的差異，進而實施相關的改進措施。

A male fighter pilot, age 34 years, had nodules in the upper apical segment of the right lung found by physical examination for 2 d.

A male fighter pilot, age 48 years, had pulmonary nodules found on physical examination for 2 d.

History of present illness

Two weeks before admission, the patient lost 10 kg due to fitness. One week before onset, he fished by the lake for 2 d. He reported occasional cough, usually accompanied by expectoration, but with no aggravation in the recent past.

Although the patient presented without fever, cough, or other symptoms, physical examination showed multiple patchy and nodular shadows in the left upper lung, so the patient was admitted to hospital for 4 d.

為了驗證本文提出的ASRS-UKF濾波算法的有效性，分別將ASRS-UKF算法、SR-UKF濾波算法以及STSR-UKF算法對上述軌跡進行跟蹤濾波。

Although the patient presented without fever, cough, or other symptoms, physical examination showed nodules in the upper apical segment of right lung, so the patient was admitted to hospital.

Pulmonary nodules were found in physical examination for 2 d, so he was admitted to hospital.

History of past illness

Enhanced preventive measures should be taken. Attention should be paid to the combination of work and rest during high-intensity flight training, the degree of fatigue and immune status of pilots, and timely arrangement of rest and recuperation. Focus should be placed on ventilation maintenance, regular ultraviolet disinfection, and chemical disinfection in working and living environment[11,12]. When necessary, indoor dryers should be added in humid environments, moldy and rotten substances cleaned up, food classified and managed, and tainted and expired food including fruits and vegetables treated. Contact with birds, cats and dogs in the working environment should be reduced. Health promotion and education should be enhanced to improve the understanding of flight surgeons and pilots on fungal infection, tuberculosis and other diseases. Chest CT scanning should be used instead of chest radiography and the image changes should be compared every year. When suspicious lesions are found, the detection of related etiology, antigen and antibody should be improved as soon as possible, and bronchoscopy should be performed when necessary. When pilots are diagnosed with tuberculosis, tuberculin test and chest CT should be carried out to screen people in the same camp to prevent collective infection[13,14]. It should be clear that patients with tuberculosis need to be isolated at home, provided with regular antituberculous therapy in sufficient doses and courses, and re-evaluated for their flight assessment after being cured. There should be concern about regular disinfection and microbiological testing of cockpits, oxygen masks, and breathing lines of pilots.

All four cases had no specific history of genetic diseases.

⑤智能收付費服務，在交通收費系統中，利用ETC設備和電子車牌等技術增強車輛收費的便利性，并詳細地展現車輛的狀態和余額情況，還能進行影像記錄；

No other abnormal health conditions were reported in the other two cases.

Personal and family history

Patient had two episodes of blood-tinged sputum 2 years ago. However, he had no fever and recovered after anti-infective therapy.

Physical examination

All four cases had no positive signs found on physical examination.

Laboratory examinations

Hemogram, C-reactive protein (CRP), erythrocyte sedimentation rate, procalcitonin, G test, mycoplasma,

, virus, tuberculosis antibody and syphilis, acquired immunodeficiency syndrome (AIDS), hepatitis C, and hepatitis B tests were all normal. T-SPOT.TB test was normal. Lymphocyte subtypes test, immunoassay, and sputum smear and culture were all normal. Cryptococcal capsular polysaccharide antigen (colloidal gold method) was positive with a titer of 1:20. Routine inspections showed that bacteria, fungi, acid-fast bacilli, cast-off cells,

pneumonia, ink staining and mycobacterial culture results were normal. Cerebrospinal fluid, blood culture, middle urine culture and fecal culture were all normal.

Hemogram, CRP, erythrocyte sedimentation rate, procalcitonin, G test, mycoplasma,

, virus, and tuberculosis antibody were all normal.

interferon- release assay was positive, tuberculin test strongly positive (+++), and sputum smear was negative.

Hemogram, CRP, erythrocyte sedimentation rate, procalcitonin, G test, mycoplasma,

, virus, and tuberculosis antibody were all normal.

interferon- release test was positive, and tuberculin test was positive (++). Sputum smear was negative. G test, GM test, cryptococcal capsular polysaccharide antigen and

IgG and IgM were all negative. T cells subsets and immunity were normal. T-SPOT.TB test was positive (A wells of 56, B wells of 4), and tuberculosis antibody was positive after examination.

電力自動化系統在電力工程中的運用，實現了系統對設備的監控，維護與管理。再結合了各種現代化通訊技術的同時，建立了一套完善的電力自動化控制系統。這其中包括對電網數據用戶，電網結構以及離線數據等多種信息的保存和處理。

第三,促進農村非正規金融與正規金融之間的有效合作。非正規金融和正規金融具有各自的比較優勢，可以用非正規金融部門的信息優勢降低正規金融部門高昂的信息搜尋成本，用正規金融機構的資金優勢彌補非正規金融組織資金不足的缺陷，共同促進農村金融體系的發展。

Imaging examinations

Chest computed tomography (CT) showed that there were multiple patchy high-density shadows in the upper lobe of the left lung, with clear boundaries, patchy high-density shadows in the edge of the focus, with CT value of 30–45 HU and enhancement after intensification, with CT value of 35–80 HU, and the larger one was about 25 mm × 20 mm; a lesion in the inferior lingular segment could be seen with blood vessel shadow passing through, the tube wall was smooth, patchy halo was seen around the lesion, and no lymph node enlargement was found in the mediastinum and hilum. Bronchoscopy showed no abnormality. Bronchoalveolar lavage was performed in the posterior segment of the left upper apex, head magnetic resonance imaging and electroencephalogram (EEG) was all normal (Figure 1A–D).

Chest CT showed that patchy and nodular shadows with increased density were found in the posterior and lingular segment of the upper lobe apex of left lung, with a small amount of bronchiectasis and thickening of the tube wall; micronodular shadow with a diameter < 3 mm was found in the posterior basal segment of the inferior lobe of left lung, with clear boundary, and no enlarged lymph nodes were found in the mediastinum and hilum. Bronchoscopy showed scar-like stenosis at the B1+2C opening in the superior lobe of the left lung, nodular protuberance on the wall of left B5 tube, uneven mucosa and positive GeneXpert in bronchoalveolar lavage fluid (Figure 1E–H).

Chest CT showed that there were several spotted and round-like shadows with increased density in the upper apex of the right lung, local induration and calcification of the lesions, which increased compared with 2019, local nodular thickening of the left oblique fissure pleura, unobstructed trachea and bronchus, and no enlarged lymph nodes in the mediastinum and hilum. Bronchoscopy showed normality, no acid-fast bacilli were found in bronchial lavage fluid, negative GeneXpert, and negative identification of delivered

species in bronchial lavage fluid (Figure 1I and J).

Chest CT showed that there were four small nodules under the pleura of the upper apex segment of the right lung, the basal segment of the lower lobe and the anterior segment of the upper lobe of left lung, with clear boundaries, the largest of which was 6 mm in diameter, the trachea and bronchus were unobstructed, and no enlarged lymph nodes were found in the mediastinum and hilus. Bronchoscopy showed no obvious abnormality, and one acid-fast bacillus was found in bronchial lavage fluid (Figure 1K).

FINAL DIAGNOSIS

Case 1

Cryptococcal pneumonia.

Case 2

Secondary pulmonary tuberculosis/upper middle (negative smear, positive GeneXpert in bronchoalveolar lavage fluid).

Case 3

Right upper lung tuberculosis, bacteria (-), GeneXpert (-).

Case 4

Right upper lung tuberculosis, bacteria (+).

TREATMENT

Case 1

He was treated with intravenous fluconazole of 400 mg for 1 d. After 18 d of treatment, fluconazole 400 mg/d was taken orally for 6 mo.

Case 2

The treatment plan was for the regimen of isoniazide (H), rifampicin (R), pyrazinamide (Z), and ethambutol (E), as 6 HRZE/6 HRE, and the course of treatment was 1 year.

Case 3

The treatment regimen was 4 HRZE/2 HRE, and the course of treatment was 6 mo.

Case 4

The treatment plan was 4 HRZE/2 HRE, and the course of treatment was 6 mo.

OUTCOME AND FOLLOW-UP

Case 1

After 18 d of fluconazole treatment, chest CT showed that the lesion was obviously reduced, cryptococcal capsular polysaccharide antigen (colloidal gold method) was positive with a titer of 1:10 and the curative effect was clear. Instead, fluconazole 400 mg/d was taken orally for 6 mo. Chest CT before and after treatment is shown below (Figure 1C and D). In the follow-up, the patient was qualified in flight test and obtained a medical waiver for flight to date without cryptococcal infection.

Case 2

由于事故是不可避免的，所以加強工作人員應對突發事件的能力與預防事故一樣重要，平時加強對事故預想演習，注重相關工作人員的應急能力的培訓，以免工作人員在發生事故時過于慌亂而使事故的負面影響更重，加大電力企業的經濟損失。

In the follow-up, the patient was qualified in flight test and obtained a medical waiver for flight without tuberculosis recurrence.

先哲孟子從道德情感與道德理性出發，論述了人與人、人與自然之間的倫理關系，即所謂“生態倫理”[19]。這就警示人們在處理各種利害關系時，不僅要建立一種審美關系，而且要建立一種倫理關系，要體現出審美與道德統一的和諧關系。

Case 3

In the follow-up, the patient was qualified in flight test and obtained a medical waiver for flight without tuberculosis recurrence.

Case 4

He was grounded after reaching the maximum flight life after being cured.

1.門檻值估計結果。由表3回歸結果可以看出，當東道國各項制度指標分別作為門檻變量帶入式(3)時，各制度指標均存在單一、顯著的“臨界值”，無雙門檻或更高階的門檻值。這說明在“一帶一路”背景下，東道國各項制度指標在影響改善東道國基礎設施的中國OFDI的東道國經濟增長效應上均有U型拐點。只有東道國的制度質量越過門檻值，中國用于改善東道國基礎設施的OFDI才能帶給東道國一定的經濟增長，否則中國的這部分直接投資將帶給東道國經濟增長負面的影響?？梢姡凇耙粠б宦贰北尘跋?，東道國制度對中國直接投資的東道國經濟增長效應有著十分重要的影響。

DISCUSSION

Specific pulmonary infections caused by fungi,

, viruses,

are common in people with impaired immune function, and the common infection route is inhaling aerosol particles containing pathogenic bacteria through the respiratory tract. Due to the lack of characteristic clinical manifestations and signs of specific pulmonary infection, misdiagnosis and missed diagnosis are easy to occur clinically and delay treatment. Specific lung infection not only aggravates the patient’s own lung infection, but also causes the spread of

and other pathogens within the air force in which naval pilots live mainly in groups, resulting in serious consequences such as noncombat attrition. Therefore, it is necessary to improve the understanding of flight surgeons about such diseases to reduce misdiagnosis and mistreatment.

Pilots are mostly young people without underlying medical conditions. After multilayer physical examination for selection and annual physical examination, most of them are people with normal immune function, so the rate of specific lung infection is low. However, if the flight training task is arduous, pilots are prone to excessive fatigue and decreased immunity, which provides opportunities for pathogens, such as fungi and

, to be inhaled and cause diseases. In this study, three fighter pilots and one helicopter pilot, aged 30–48 years, were diagnosed and treated for lung infections. The causes of the cryptococcal infection in Case 1 were analyzed as follows: (1) Deliberate weight loss through fitness during flight training, leading to a decrease in immunity from excessive fatigue and rapid weight loss; and (2) A large number of chickens and ducks can be found in the humid environment by the lake where the patient fished for 2 d before the onset of the disease, although there was no clear contact history with the birds.

At present, the routine physical examination of pilots is mainly chest radiography, which may lead to missed diagnosis of some early small lesions. Therefore, it is necessary to suggest that the annual physical examination of pilots adopt thin-layer chest CT plain scan, especially at the stage of selecting pilots. The chest CT in Case 1 showed multiple patchy shadows, halo sign at the edge, visible air bronchogram, blood vessels passing through the lesions, and small holes in the treatment process, which accorded with the imaging findings of cryptococcal pneumonia[4]. Case 2 showed multiple patches and nodular changes in the posterior segment of the upper apex with bronchiectasis on CT, and bronchoscopy showed lesions in the bronchial mucosa, which were consistent with tuberculosis[5]. Attention should be paid to strengthening the follow-up mechanism and compare the changes in lesions on CT every year. In Case 3, chest CT demonstrated that the right upper apical pulmonary nodules were larger than 2 years ago, and the old and new nodules coexisted with calcification, which was in line with the imaging characteristics of tuberculosis. After positive T-SPOT.TB examination, pulmonary tuberculosis was clinically diagnosed[6]. For suspicious lesions, those with atypical imaging manifestations should improve the detection of bacteria, fungi,

, viruses and other pathogens and antigens. Case 1 was diagnosed with repeated positive capsular antigen detection and titer detection of

[5,6]. Bronchoscopy can be improved when there are no cough and expectoration symptoms, and bronchial lavage fluid is inspected for pathogens. In Case 4, a small number of acid-fast bacilli was found in bronchial lavage fluid, and in Case 2, airway lesions were found under bronchoscopy, and GeneXpert is positive, so tuberculosis was diagnosed[7]. All four cases in this group had no obvious symptoms and signs, and abnormalities were found after chest CT scanning during physical examination. The final diagnosis was made after improving the detection of pathogens, antigens, and antibodies and bronchoscopy with bronchoalveolar lavage. Timely improvement of auxiliary inspection and early diagnosis are the key to ensuring flight safety.

has neurotropic characteristics, and it is necessary to further check whether there is central nervous system infection after cryptococcal pneumonia is diagnosed. The treatment of cryptococcal infection is mainly based on the Guidelines for the Management of Cryptococcal Disease of Infectious Diseases Society of America (IDSA) in 2010[8], and the treatment is graded according to evaluation of immune status, systemic dissemination and severity of respiratory symptoms, with a course of treatment of 6–12 mo. The standard treatment of pulmonary tuberculosis (4 drugs for fortification period, 2 or 3 for consolidation period) lasts for 6–12 mo[9,10]. Sufficient dose and course of treatment are recommended during the treatment, and hepatic and renal function and chest CT are reexamined every month to evaluate the curative effect and side effects of the drugs. Regular reexamination is still needed after cure to prevent recurrence.

Hemogram, CRP, erythrocyte sedimentation rate, procalcitonin, G test,

,

, virus, and tuberculosis antibody were all normal.

interferon- release test was positive, and tuberculin test was positive (++). Sputum smear was negative.

The hidden onset and long course of treatment of specific pulmonary infections caused by fungi and

are seriously harmful to the combat effectiveness of naval pilots. Flight surgeons at all levels should pay attention to the following clinical aeromedical points.

通過本院自行設定的調查問卷對兩組護理人員對職業防護知識的知曉情況及職業防護行為執行情況進行觀察和評定,其中職業防護知識知曉率主要調查內容為心理損傷、物理損傷、化學損傷、生物損傷等,其中回答正確率≥90%表示熟悉,回答正確率在50%-89%之間表示掌握,<50%表示了解;職業防護行為則從有無正確佩帶口罩、手套、有無規范吸收、有無準確登記報告艾滋病職業暴露、有無在銳器刺傷手后及時擠血和流水沖洗等方面進行調查,同時統計清洗滅菌合格率。

Patient had a smoking history of 25 cigarettes per day for 13 years.

八五○農場的實測平均水田灌水量405 mm，降水補給外的補給為水田灌溉補給，補給量為107.4 mm,補給系數為26.5%。

CONCLUSION

The infection rate of specific lung infection in pilots is low. Due to the lack of characteristic clinical manifestations, misdiagnosis can occur easily. Specific lung infection not only aggravates the pilots’ health, but also causes the spread of pathogens in air forces, with serious consequences. Chest CT scanning should be used instead of chest radiography in pilots’ physical examination. When pilots are diagnosed with specific lung infection, relevant tests and chest CT scanning should screen people in the same camp. After active treatment, most pilots with specific pulmonary infection can be cured and return to flight.

FOOTNOTES

Zeng J and Zhao GL contributed equally to this work; Zeng J and Dong J designed the research; Zeng J, Yi JC, Liu DD, Jiang YQ, Lu X, Liu YB, and Xue F collected and analyzed the clinical data; Zeng J, Yi JC, and Zhao GL wrote the manuscript; Zeng J and Dong J revised the manuscript.

Key Project of Medical Service Scientific Research of Navy Medical Center, No. 20M2302.

Informed written consent was obtained from the patients for the publication of this report and any accompanying images.

The authors declare that they have no conflict of interest.

The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).

采用同樣的方法可計算出血壓、脈搏、呼吸、尿量、意識狀態（CS）、末梢循環（PC）、血常規（RBT）、血生物化學（BE）、凝血酶原時間（PT）的信息增益率：

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

China

Jia Zeng 0000-0001-5201-4526; Guo-Li Zhao 0000-0002-0017-6729; Jia-Cheng Yi 0000-0021-9413-0801;Dan-Dan Liu 0000-0003-1947-2369; Yan-Qing Jiang 0000-0012-3824-9462; Xiang Lu 0000-0002-8128-7718; Yan-Bing Liu 0000-0002-1171-8314; Fei Xue 0000-0002-2947-9269; Jie Dong 0000-0021-8118-7718.

Chen YL

4.1 生產工藝水平落后 兵團農機企業生產工藝落后、核心部件加工能力差，形成了低價競爭的市場環境，而中高端犁市場被國外進口犁占有。有部分企業生產中高端犁具，核心工作部件如犁體等依賴進口，利潤空間低，對自身技術的提升作用微乎其微。

Kerr C

Chen YL

1 Alves VS, Leite-Aguiar R, Silva JPD, Coutinho-Silva R, Savio LEB. Purinergic signaling in infectious diseases of the central nervous system.

2020 ; 89 : 480 -490 [PMID: 32717399 DOI: 10 .1016 /j.bbi.2020 .07 .026 ]

2 Jiang XQ, Zhang YB. Cryptococcal pneumonia in a human immunodeficiency virus-negative patient: A case report.

2020 ; 8 : 2038 -2043 [PMID: 32518798 DOI: 10 .12998 /wjcc.v8 .i10 .2038 ]

3 Wang N, Li T, Du X, Li Y, Sun M, Huan S, Zhang H, Wang L, Chen M, Huang F, Zhao Y. Effectiveness of the Integrated TB Surveillance System - China, 2018 -2019 . China CDC Wkly 2020 ; 2 : 190 -193 [PMID: 34594621 ]

4 Obmann VC, Bickel F, Hosek N, Ebner L, Huber AT, Damonti L, Zimmerli S, Christe A. Radiological CT Patterns and Distribution of Invasive Pulmonary Aspergillus, Non-Aspergillus, Cryptococcus and Pneumocystis Jirovecii Mold Infections - A Multicenter Study.

2021 ; 193 : 1304 -1314 [PMID: 34034346 DOI: 10 .1055 /a-1482 -8336 ]

5 Yan C, Wang L, Lin J, Xu J, Zhang T, Qi J, Li X, Ni W, Wu G, Huang J, Xu Y, Woodruff HC, Lambin P. A fully automatic artificial intelligence-based CT image analysis system for accurate detection, diagnosis, and quantitative severity evaluation of pulmonary tuberculosis.

2021 [PMID: 34842959 DOI: 10 .1007 /s00330 -021 -08365 -z]

6 Liu Y, Yao L, Wang F, Sun Z, Tan Y, Sha W. The TBAg/PHA ratio in T-SPOT.TB assay has high prospective value in the diagnosis of active tuberculosis: a multicenter study in China.

2021 ; 22 : 165 [PMID: 34074288 DOI:10 .1186 /s12931 -021 -01753 -5 ]

7 Kaso AW, Hailu A. Costs and cost-effectiveness of Gene Xpert compared to smear microscopy for the diagnosis of pulmonary tuberculosis using real-world data from Arsi zone, Ethiopia.

2021 ; 16 : e0259056 [PMID: 34695153 DOI: 10 .1371 /journal.pone.0259056 ]

8 Gassiep I, Douglas J, Emeto TI, Crawley K, Playford EG. Cryptococcal infections over a 15 year period at a tertiary facility & impact of guideline management.

2018 ; 61 : 633 -638 [PMID: 29663539 DOI: 10 .1111 /myc.12783 ]

9 Padmapriydarsini C, Mamulwar M, Mohan A, Shanmugam P, Gomathy NS, Mane A, Singh UB, Pavankumar N, Kadam A, Kumar H, Suresh C, Reddy D, Devi P, Ramesh PM, Sekar L, Jawahar S, Shandil RK, Singh M, Menon J, Guleria R;METRIF Team. Randomized trial of Metformin with Anti-tuberculosis drugs For Early Sputum Conversion in Adults with Pulmonary Tuberculosis.

2021 [PMID: 34849651 DOI: 10 .1093 /cid/ciab964 ]

10 Syburra T, Nicol E, Mitchell S, Bron D, Rosendahl U, Pepper J. To fly as a pilot after cardiac surgery.

2018 ; 53 : 505 -511 [PMID: 29040454 DOI: 10 .1093 /ejcts/ezx346 ]

11 Lin J, Yan D, Fu J, Chen Y, Ou H. Ultraviolet-C and vacuum ultraviolet inducing surface degradation of microplastics.

2020 ; 186 : 116360 [PMID: 32896740 DOI: 10 .1016 /j.watres.2020 .116360 ]

12 Kühn KP, Chaberny IF, Massholder K, Stickler M, Benz VW, Sonntag HG, Erdinger L. Disinfection of surfaces by photocatalytic oxidation with titanium dioxide and UVA light.

2003 ; 53 : 71 -77 [PMID: 12892668 DOI:10 .1016 /S0045 -6535 (03 )00362 -X]

13 Creswell J, Khan A, Bakker MI, Brouwer M, Kamineni VV, Mergenthaler C, Smelyanskaya M, Qin ZZ, Ramis O, Stevens R, Reddy KS, Blok L. The TB REACH Initiative: Supporting TB Elimination Efforts in the Asia-Pacific.

2020 ; 5 [PMID: 33114749 DOI: 10 .3390 /tropicalmed5040164 ]

14 Garcia R, Spiegel JM, Yassi A, Ehrlich R, Rom?o P, A Nunes E, Zungu M, Mabhele S. Preventing Occupational Tuberculosis in Health Workers: An Analysis of State Responsibilities and Worker Rights in Mozambique.

2020 ; 17 [PMID: 33081345 DOI: 10 .3390 /ijerph17207546 ]