This review is an update and continuation of reports on invasive procedures employed in the Russia with questionable clinical indications, including those performed primarily for research [1-3]. A conclusion was that one of the motives to overuse invasive methods was personnel training, among others, with the purpose of readiness for war. Attention is directed here to bronchoscopy (Bs) in patients with asthma, utilized despite the prevailing opinion that it offers minimal benefits if any. Besides, the use of Bs in bronchitis and tuberculosis (Tb) is briefly delineated. Some newest Russian-language textbooks are based on the international literature thanks to the Internet resources. However, earlier manuals contained recommendations partly at variance with internationally accepted ones. A return to some invasive procedures has been noticed in surgery since the start of the Ukraine war in 2022; overviewed in. Therefore, this review is relevant for the clinical practice now as before.

The international literature does not indicate any specific role of Bs in asthma diagnosis and treatment, while asthmatics face a higher risk of complications from this procedure. Indications for Bs in asthma include ongoing wheezing that does not respond to bronchodilators and other treatments. The typical reason for Bs is to seek other potential causes of the symptoms. Bs is generally recommended when other sources of diagnostic information are exhausted [4,5]. In a comprehensive handbook on asthma, clinical indications for Bs are not mentioned [6]. In specific situations, bronchial lavage may be warranted for severe asthma [7,8]. Clinical guidelines are not addressed here [9].

Recent Russian-language textbooks draw on international literature from online resources. Some earlier manuals included recommendations that were inconsistent with internationally recognized ones. In patients with asthma, the aim of Bs was described as identifying potential links between the disease and infection, as well as clarifying the nature of inflammatory lesions [10,11]. The concept persisted for long time that a cause of asthma is a focus of inflammation; and the purpose of Bs was declared to be a search for that focus [12,13]. The presence of abundant secretion or mucopurulent sputum in a child was suggested as an indication for Bs with biopsy in order to assess endobronchial inflammation [14]. Mucus accumulation in the bronchi was considered a reason for repeated Bs in asthma [15]. The seminal monograph indicated that Bs is advisable “almost for all subacute and chronic respiratory diseases” in children [11]. Conditions such as asthma, Tb (also if suspected), bronchitis, suspected pulmonary or bronchial inflammation, dyspnea and prolonged coughing, have been proposed as indications for Bs [15-22]. Coughing longer than 4-6 weeks and changed character of coughing in a smoker are regarded as absolute indications [22]. Bs was used and recommended for children and adults with asthma during periods of both remission and exacerbation, in cases with mild to severe course of the disease [15,23-31], as well as in bronchitis accompanied by bronchospasm and/or allergy [23,29]. Bs was considered as an early diagnostic tool for various forms of asthma, and was employed repeatedly for observation [15,28]. Some specialists conducted as many as 15 Bs per course in pediatric asthma [32]. Of note, Bs in asthma was found to cause complications more often than in other respiratory conditions. Nevertheless, the same specialists conducted ~400 Bs in 200 asthma patients, leading to no changes in diagnoses [33].

The widening of indications for Bs owes to Lev Ioffe and Fedor Uglov [13,34-38]. In a published guideline, Ioffe instructed that “Bs should be conducted in all pulmonary diseases” [34]. Uglov discussed ~7500 Bs carried out at his facility both in children and in elderly, mainly with inflammatory conditions like bronchitis, pneumonia and asthma (524 cases), focusing on monitoring of inflammation in the airways [13,36]. The conclusion was that Bs is crucial for the diagnosis of nearly all lung diseases, being advisable also at early stages. Based on the bronchoscopic findings, decisions were taken on indications for subsequent therapeutic Bs [36]. Following a series of Bs, resections of segments or lobes, considered by operators to be abnormal, were performed. This was designated as a radical treatment of asthma [13]. More details and references are in [3,9]. The efficacy of therapeutic bronchoscopy in moderate bronchitis was highlighted by Uglov et al., who performed up to 6 Bs for each therapeutic course [37]. Specifically, signs of mucosal atrophy (atrophic bronchitis) were considered a sufficient reason to perform Bs [15].

Following the above-named leading experts, numerous Bs have been conducted on children and adults with non-specific respiratory diseases at provincial hospitals and outpatient facilities [37]. In particular, difficulties with local anesthesia, requiring general anesthesia in up to 25% of patients in order to examine trachea and bronchi, have been reported. Challenges at bronchial biopsy under local anesthesia were noticed as well [39]. Asthmatic patients faced significant technical difficulties associated with Bs [40]. Substantial discomfort may have arisen from those “technical difficulties” without any benefit to some patients. Certainly, Bs has been performed according to indications in many cases, being often life-saving (extraction of foreign bodies etc.). However, the method was known to be overused in research and practice. Repeated Bs in children under local anesthesia caused psychological stress and resulted in harm to teeth, larynx and bronchi [41]. It was evident for inside observers that broad adoption of endoscopy took place following a directive. The involvement of authorities in research and practice has been known to occur in the former Soviet Union. Health care officials preferred methods suitable en masse for large diagnostic categories of patients [3]. Besides, as mentioned above, a motive to overuse invasive procedures was the personnel training. As a result of the authoritative management approach, suboptimal methods have been employed and persisted for long periods.

Laser therapy was administered to children and adults by means of Bs for asthma, chronic pneumonia and bronchitis [42-46], including mucosal atrophy (atrophic bronchitis), in some cases related to ionizing radiation [42,47-49]. Like other types of electromagnetic rays, laser at lower power densities produces heat, while at higher energies it can damage tissues. From the perspective of general pathology, atrophy would progress in consequence of repeated injury. In the international literature, main indications for laser bronchoscopy are tumors and tracheal stenosis. Emergency laser treatment is applied in hemoptysis [50]. Furthermore, bronchoscopic insufflations of nitric oxide (NO) have been used for the treatment both of Tb and of non-specific inflammatory conditions [51-53]. The method has been presented in the instructive “National Manual” [22]. We have found in the international literature no reports on the use of NO via bronchoscope, only per inhalation [54].

Both flexible and rigid bronchoscopes have been applied and recommended in chronic bronchitis and asthma both in children and in adults [14,55,56]. For acute pneumonia in children, Bs was intended to evaluate the character of inflammation of the bronchial mucosa. In chronic pneumonia, Bs was deemed essential for the same reason as well as to exclude Tb and congenital abnormalities [10]. In some recent publications, Bs has been recommended for pediatric pneumonia and other inflammatory conditions with duration ≥4 weeks [21,57,58]. Another questionable indication has been a round lesion in the lung [18,21,22,57,59-61]. Despite the advancement in Bs technique, its diagnostic yield in pulmonary nodules remains inferior to that of trans-thoracic needle aspiration [62]. Another “shot over the target” is a sweeping recommendation to perform Bs in all patients with suspicion of “chronic non-specific” or obstructive pulmonary disease [63,64].

Here follow some more examples of excessive use of endoscopy, also for research. Bs served in the secondary screening phase for chronic non-specific respiratory diseases (bronchitis, asthma and others), diagnosed in ~4% of children living in industrially polluted areas of Moscow province [65]. Bs was a screening tool for workers exposed to dust; it was applied both in healthy individuals and in those suffering from rhinitis or bronchitis, sometimes repeatedly for monitoring of natural history [66,67]; generally in bronchitis including its atrophic variety; in acute and chronic pneumonia [15,68-71], e.g. in conscripts suspected to have pneumonia (~1500 Bs in 1000 patients) [72]. A series of studies with the overuse of cystoscopy and biopsy in connection with the overdiagnosis of malignant and precancerous urinary bladder lesions [73] has been commented previously [74]. We don’t know whether and how many cystectomies followed the overdiagnosis but there have been cystoscopies and “mapping biopsies” without sufficient indications [73]. This example of overdiagnosis and overtreatment was noticed at the XXIII Congress of the International Academy of Pathology,15-20 October 2000 in Nagoya, Japan [75]; commented in [74].

Gordeeva and Sivokozov (2020) applied and recommended Bs with biopsies for end stage renal disease [76]. Gastrodoudenoscopy was used in the same condition without clear benefit for patients [38]. Furthermore, lavage fluid obtained through Bs from individuals with lung cancer and those with Tb (including solitary tuberculoma) was analyzed by infrared spectroscopy for research with no comprehensible implications for theory and practice [77]. Bronchial biopsies were gathered from patients with known lung cancer, whereas the quality of histological images was poor [49], causing discomfort for the patients without impacting the therapy. Certain histopathological descriptions have been questionable, such as the “atrophy development” of bronchial mucosa in asthma patients including children; for example, atrophy of various degree was reportedly found in ~80% of individuals ≥12 years old [55].

Excessive surgical radicalism in Tb has been discussed in [3]. Bs was applied in all forms of Tb across various institutions and research groups including localized forms (tuberculoma) [78-85]; it was used in young patients with “hyperergic tuberculin tests” [86], or as a part of the diagnostic workout for suspected Tb cases with sputum negative for Mycobacteria. Over the period 1995-2015, the average number of therapeutic Bs per one Tb patient increased from 2 to 5.6 [53]. The important role of Bs in diagnostics and monitoring of Tb has been stressed now as before [18]. Primary Tb in children (including small ones) was seen as an indication for Bs [10]; although there are less invasive diagnostic methods such as the gastric aspiration and induced sputum [87-89]. For cases of destructive Tb, the Health Ministry recommended therapeutic Bs up to 32 procedures per course [90]; whereas the principle of informed consent has not always been followed. Extended indications for Bs and thoracic surgery have been claimed for patients with diagnosed or suspected Tb (including smear-negative cases) combined with alcohol use disorders. Endoscopic and other biopsies have been taken from alcoholics for research; overviewed previously [3,91].

Bs served as a screening tool for Tb in patients with prolonged low-grade fever, both with positive and negative tuberculin tests [92]. Other studies employed Bs as a second-step screening technique for Tb in children [93]. Endoscopic evaluation of treatment outcomes has been utilized in pulmonary Tb cases with non-specific bronchial lesions [15,59,61,94]. Of note, the international literature suggests that in smear-negative Tb, bronchoscopy's role should be confined to patients who do not respond to therapy and/or those with a strong suspicion of an alternative diagnosis [62].

The pediatric clinic of the Sechenov Medical University in Moscow is a prominent institution known for authoring textbooks and applying endoscopic techniques extensively for diagnostic, therapeutic, and research purposes, especially during Dr. Isaeva's tenure as department head (1970-1991) [10,95]. As previously mentioned, Bs was applied in children with pneumonia, bronchitis and asthma [96,97], while complications have been observed [98]. In particular, endoscopy with biopsy was broadly used for studies of autoimmune conditions [65,99-103].

As noted earlier, bronchial biopsy samples have been used for research, though certain histological samples were of low quality, with morphometric and other quantitative parameters changing as expected [49,104]. For example, molecular and histochemical markers of inflammation were influenced in a similar way both by medical and surgical treatments of bronchial asthma [105]. Manipulations with numerical data have been proven in some cases; documentary evidence and references are in the book [3].

The concept of informed consent was not always adequately understood and followed; corresponding statements appeared only in recent publications. For example, in a research where Bs was carried out on children with moderate to severe asthma, informed consent was acquired from parents or guardians [106], who could have been misinformed about indications. There has been a stereotype: post-graduate students and doctoral candidates came to Moscow and other centers from different parts of the former Soviet Union, some of them paying for preparation of specimens, literature review, etc. Certain researchers planning emigration completed their dissertations under time pressure. Among others, invasive methods were sometimes applied without sufficient clinical indications in conditions of suboptimal procedural quality assurance.

Some bronchoscopic methods applied for diagnostics and therapy have been patented; several examples follow. Therapy monitoring of chronic catarrhal bronchitis by means of repeated examinations of bronchial washings obtained by Bs every other day during the whole period of treatment [107]; laser therapy via bronchoscope of “atrophic bronchitis deformans”; bronchitis diagnostics in children and adults [108-110], treatment of pulmonary Tb by endobronchial instillations of surfactant-containing preparations produced from bovine lung or human amniotic fluid every other day during 3-8 weeks [111]; discussed previously [112]. Of note, exogenous surfactant may have sense within aerated alveoli; while in bronchi it is a foreign substance that must be expectorated by the patient.

Some recommendations cited here are not new; but excessive use of invasive procedures seems to be on the increase these days [3,9]. As mentioned above, the average number of therapeutic Bs per one Tb patient increased from 2 to 5.6 in the period 1995-2015 [53]. The surgical activity in Tb has increased as well, while some indications have been doubtful [3,91]. Of note, invasive methods such as endoscopy for research without adequate clinical indications are governed by the Declaration of Helsinki. In any event, such studies require informed consent. Children need special protection. When a child or adolescent is able to give assent for participation in a study, it should be acquired alongside the consent from parents or caregivers [113,114]. Adolescents are in a sense between children, who are to be treated according to their best interests represented by parents or caregivers, and independent adults, who are to be treated according to their wishes. There is usually no prescribed “age of consent”, but a condition, implying the capacity for understanding. Like adults, mature minors should enjoy confidentiality and the right to treatment according to their wishes [114]. In the author’s opinion, Bs merely for research should not exist; it must be implemented according to clinical indications. Practical recommendations must be based on reliable and reproducible research. Only such research should be included into reviews and meta-analyses.

According to an estimate from the United States, ≥30% of endoscopies performed in some clinical settings had questionable indications [115]. In Russia, some invasive methods with doubtful indications were introduced or advocated by first generation military surgeons [3]. The Soviet period brought about an expansion of admission numbers to universities and medical educational institutions, sometimes with little regard for the quality of the academic preparation of students [116]. One of the motives to overuse invasive procedures has been personnel training, among others, with the objective of readiness for war. Note that military and medical ethics are not the same. The comparatively short life expectancy in Russia is a strategic advantage as it necessitates less healthcare investments and pensions. Furthermore, among factors contributing to the use of invasive procedures with doubtful indications is the partial isolation from international scientific community, insufficient consideration of the principles of professional autonomy, informed consent and scientific polemics, as well as paternalistic attitude to patients.

Ethical and legal basis of medical practice and research has not been sufficiently known and observed in Russia. The term “deontology” is often used for medical ethics in this country. Textbooks and monographs on deontology explained the matter somewhat vaguely, with truisms and generalities but not much practical guidance. Today, the growing economy enables acquisition of modern equipment; and medical research is on the increase. Under these circumstances, the purpose of this review is to remind that, performing invasive procedures, the risk-to-benefit ratio must be kept as low as possible. Insufficient coordination of medical studies and partial isolation from the international community can result in parallelism in research, unnecessary experimentation, and application of invasive procedures without sufficient indications. Considering shortcomings of medical practice, research and education, governmental directives and increase in funding are unlikely to be a solution. Measures for improvement of the healthcare in Russia must include participation of authorized foreign advisors. 

Declaration

No conflict of interest.

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