Male secretory breast cancer: case in a 6-year-old boy with a peculiar gene duplication and review of the literature.

PURPOSE: Secretory breast cancer (SBC) is one of the rarest breast cancer (BC), representing the majority of BC in childhood. Nevertheless, it elicits a lot of interest both for the peculiar morphology and the characteristic genetic features. Currently, there is no consensus on optimal treatment strategy. Therefore, it is useful to report every case in order to establish treatment algorithms. METHODS: We describe the case of a 6-year-old boy diagnosed with a SBC, with peculiar genomic and immunohistochemical features. Moreover, we carried out a review of the literature in order to analyze the present state of knowledge about this rare entity. RESULTS: To the best of our knowledge, there are only 120 cases published in literature, only 32 in males and only 2 younger than 6 years. Furthermore, this one had peculiar genomic and immunohistochemical features. Indeed, even if SBC expresses basal-cell markers, our patient had a triple-negative tumor expressing both basal and luminal cell markers. Furthermore, the boy's genomic profile revealed not only positivity for the typical SBC's translocation t(12;15), but also for a 3q28 duplication, found in his father (healthy) and paternal grandfather (with a previous BC). None were positive for BRCA mutation. This locus includes only one gene encoding for a growth factor recently linked to Early Infantile Epileptic Encephalopathy-47 and Idiopathic ventricular tachycardia. Even if the literature does not provide evidence of a pathogenic role it is not possible to exclude a cancer-predisposing activity. CONCLUSIONS: SBC is a rare type of BC, characterized by triple-negative features with an unexpectedly good prognosis. More data are needed to fully understand the behavior of this cancer and genomic profiling could be helpful in improving its diagnosis and management.

Railway noise annoyance modeling: Accounting for noise sensitivity and different acoustical features.

Noise annoyance due to railway traffic is a growing issue in today's society. This annoyance may be predicted using noise-exposure relationships with mean energy-based index. However, there is room for improvement of models as other acoustical and non-acoustical factors also influence noise annoyance responses. In this paper, it is proposed to highlight annoying auditory sensations evoked by the railway noise and determine acoustical and psychoacoustical indices combined in a predictive model. A laboratory experiment involving railway pass-by noise in urban areas was carried out. Annoyance ratings, noise sensitivity ratings, and free verbalization data were gathered. The analysis underlined annoying auditory sensations caused by railway pass-by noises. Two indices were proposed to account for irregular amplitude fluctuation and noise event duration-related sensations. A multilevel regression analysis was conducted, leading to two annoyance models considering noise indices and noise sensitivity. These models were finally compared to a similarly obtained multilevel regression model related to tramway noise annoyance. The comparison was carried out as a cross-validation considering the models and the respective datasets collected in laboratory conditions for model construction. Results showed that the railway noise annoyance model led to a good prediction of tramway noise annoyance and vice versa.

Assessment of annoyance due to urban road traffic noise combined with tramway noise.

Due to the expansion of urban areas, an increasing number of residents are exposed to combined community noise sources. Studies show that the exposure to transportation noise significantly affects health and well-being. Noise annoyance is one of these adverse health effects. Up to now, annoyance due to transportation noise is mostly assessed considering single noise exposure situations neglecting the effects of potential interactions between noise sources. In this study, perceptual phenomena involved in noise annoyance due to combined urban road traffic and tramway noises are assessed in laboratory conditions with imaginary and simulated contexts. The urban road traffic was composed of light vehicles, heavy vehicles, buses, and powered-two-wheelers in different driving conditions. The tramway traffic corresponded to tramways in in-curve operating configurations. It could be shown that the road traffic and tramway traffic partial annoyance responses were influenced by each other. Throughout the experiments the strongest component effect prevailed but secondary phenomena could also be observed. Considering the perceptual phenomena highlighted in the analysis, it is shown that total noise annoyance due to the combined noises can be most adequately predicted by the strongest component model. This result was obtained by calculating partial annoyance responses due to urban road and tramway traffic.

Spectral and modulation indices for annoyance-relevant features of urban road single-vehicle pass-by noises.

The models that relate noise annoyance assessments to noise signal parameters are mainly based on energy-related indices (e.g., LDEN). However, various studies have shown that sound characteristics of environmental noises linked to temporal and spectral signal features also influence noise annoyance responses. In order to enhance noise annoyance models, an adequate perception-related characterization of these influential acoustical features is essential. On the basis of urban road single-vehicle pass-by noises, this study will show the identification of noise characteristics that rely on spectral and temporal signal properties and that are related to noise annoyance. Based on a semantic differential test with a verbalization task, it will be shown that the sensation dull/shrill, related to the spectral content of the noises and the modulation-related sensations sputtering and nasal are linked to annoyance. The sensation dull/shrill could be characterized using the index TETC (Total Energy of Tonal Components within critical bands from 16 to 24 barks). The correlation of sputtering and nasal sensations with psychoacoustic indices was unsatisfactory. Two alternative indices are proposed to improve the characterization of these specific sensations. It is shown that noise annoyance assessment benefits from taking the TETC index and the sputtering and nasal indices into account.

Anaphylaxis to diclofenac: nine cases reported to the Allergy Vigilance Network in France.

Nine cases of diclofenac hypersensitivity recorded by the Allergy Vigilance Network in France from 2002 to 2012 were studied. Data from history, symptoms, skin tests, basophil activation tests, and oral challenge (OC) were recorded. Grade 3 severe anaphylactic reactions occurred in seven cases of nine. IgE-dependent anaphylaxis was confirmed in six cases: positive intradermal tests (n = 4), a syndromic reaction during skin tests (n = 1), and one case with grade 1 reaction and negative skin tests had an anaphylactic shock to the OC. A nonimmune reaction was suspected in one case. An IgE-dependent mechanism may be the predominant cause of adverse reactions to diclofenac. Allergy skin tests must be carried out sequentially at the recommended concentrations. BATs may be helpful because they can support the diagnosis of anaphylaxis. Given the risks of a direct challenge to diclofenac, OC to aspirin should be performed first to exclude a nonimmunologic hypersensitivity to NSAIDs. Tests for specific IgEs to most frequently used NSAIDs such as diclofenac and ibuprofen are urgently needed.

Beyond activity patterns: The complex process of activity management among individuals with chronic musculoskeletal pain after an orthopaedic trauma.

CONTEXT: Individuals must change the way they perform activities in response to chronic pain. In the literature, three activity patterns are commonly described: avoidance, pacing, and persistence. Many studies have explored these activity patterns. However, little research has delved into the factors that lead people to adopt a particular activity behaviour. This study aimed to explore the relationship that people with chronic musculoskeletal pain have with activity and highlight the factors underlying their practices. METHODS: The qualitative study was conducted by researchers in the social sciences, physiotherapy, psychology, and rehabilitation medicine. Observations of vocational workshops and semi-structured interviews were conducted with 33 persons undergoing rehabilitation for chronic musculoskeletal pain after an accident. RESULTS: Patients' declarations and actions show that any one patient will alternate between activity patterns: the same person may adopt a strategy of avoidance, pacing or persistence depending on the context, the importance of the activity, personal objectives, and representations of self, pain, and activity. The decision to engage in a particular behaviour is based on a process of self-negotiation weighted by the circumstances, the nature of the activity, the importance attached to it, and the individual's perceived ability. CONCLUSION: Our study emphasized the complexity of physical, social, and contextual factors that intervene in the relationship toward activity. Rather than favouring pacing, the therapist's role in rehabilitation might be to reinforce the reflexive process and the patient's adaptability in approaching the activity, to foster the capacity to find flexible solutions. SIGNIFICANCE: Patients choose an activity pattern (avoidance, pacing, persistence) according to the challenges they face in their daily lives. Context, representations of self and activity, as well as goals sought influence these choices. Some patients report having learned to adapt their activity management strategies. Therefore, therapeutic approaches in the rehabilitation context could focus on these adaptive capacities to offer patients optimal pain and activity management and develop their ability to use different strategies according to the circumstance.

Identification of enolases and aldolases as important fish allergens in cod, salmon and tuna: component resolved diagnosis using parvalbumin and the new allergens.

BACKGROUND: The majority of fish-allergic patients are sensitized to parvalbumin, known to be the cause of important IgE cross-reactivity among fish species. Little is known about the importance of fish allergens other than parvalbumin. OBJECTIVE: The aim of this study was to characterize hitherto undefined fish allergens in three commonly consumed fish species, cod, salmon and tuna, and to evaluate their importance for in vitro IgE-diagnosis in addition to parvalbumin and fish gelatin. METHODS: Sixty-two patients were diagnosed by clinical history, skin prick tests and specific IgE to fish extracts. Two new fish allergens from cod, salmon and tuna were identified by microsequencing. These proteins were characterized by immunoblot, ELISA and mediator release assay. Purified parvalbumin, enolase, aldolase and fish gelatin were used for quantification of specific IgE in ELISA. RESULTS: Parvalbumin and two other allergens of 50 and 40 kDa were detected in IgE-immunoblots of cod, salmon and tuna extracts by most patient sera. The 50 and 40 kDa proteins were identified as beta-enolase and fructose-bisphosphate aldolase A respectively. Both purified enzymes showed allergenic activity in the mediator release assay. Indeed, 72.6% of the patients were sensitized to parvalbumin, 20% of these had specific IgE to salmon parvalbumin only. IgE to enolases were found in 62.9% (0.5-95.0 kUA /L), to aldolases in 50.0% (0.4-26.0 kUA /L) and to fish gelatin in 19.3% (0.4-20.0 kUA /L) of the patients. Inter-species cross-reactivity, even though limited, was found for enolases and aldolases by IgE-inhibition ELISA. CONCLUSIONS AND CLINICAL RELEVANCE: Fish enolase and aldolase have been identified as important new fish allergens. In fish allergy diagnosis, IgE to enolase and aldolase are especially relevant when IgE to parvalbumin are absent.

Total annoyance from an industrial noise source with a main spectral component combined with a background noise.

When living close to an industrial plant, people are exposed to a combination of industrial noise sources and a background noise composed of all the other noise sources in the environment. As a first step, noise annoyance indicators in laboratory conditions are proposed for a single exposure to an industrial noise source. The second step detailed in this paper involves determining total annoyance indicators in laboratory conditions for ambient noises composed of an industrial noise source and a background noise. Two types of steady and permanent industrial noise sources are studied: low frequency noises with a main spectral component at 100 Hz, and noises with a main spectral component in middle frequencies. Five background noises are assessed so as to take into account different sound environments which can usually be heard by people living around an industrial plant. One main conclusion of this study is that two different analyses are necessary to determine total annoyance indicators for this type of ambient noise, depending on the industrial noise source composing it. Therefore, two total annoyance indicators adapted to the ambient noises studied are proposed.

Molecular allergology in practice: an unusual case of LTP allergy.

The authors describe an unusual case of LTP allergy. A 35 years old patient presented repeated episodes of angiooedema after food intake and complained 10 years ago of contact urticaria and rhinoconjunctivitis when exposed to cannabis leaves and to marijuana smoke. The suspected responsible foods, such as wheat flour in bread, are known to contain LTR Oral syndrome occurred after ingestion of walnuts. Cutaneous tests confirmed immediate responses to several flours and nuts and also to cannabis leaf and flower. A few months later he had similar accidents following peach ingestion and drinking of beer and several wines which all induced positive skin tests. Serological investigations using ImmunoCAP and ISAC microarray confirmed IgE positivity for n Pru p3, r Cor a 8 and n Art v3. It was assumed that sensitization to LTP, the major allergen of cannabis, was responsible of the primary sensitization and induced further LTP food allergies.

Clinical characteristics of and outcomes for patients with COVID-19 and comorbid lung diseases primarily hospitalized in a conventional pulmonology unit: A retrospective study.

BACKGROUND: Scant data are currently available about a potential link between comorbid chronic lung diseases (CLD) and the risk and severity of the coronavirus disease 2019 (COVID-19) infection. METHODS: To describe the clinical characteristics of and outcomes for patients with COVID-19 infection, including patients with comorbid respiratory diseases, who have been primarily hospitalized in the pulmonology department of Strasbourg University Hospital, France. In this retrospective, single-center study, we included all confirmed cases of COVID-19 from March 3 to April 15, 2020. We then compared the symptoms, biological and radiological findings, and outcomes for patients with and without CLD. RESULTS: Of the 124 patients that were enrolled, the median age was 62 years, and 75 patients (60%) were male. Overall, 40% of patients (n=50) had preexisting CLD, including chronic obstructive pulmonary disease (COPD) (n=15, 12%) and asthma (n=19, 15%). Twenty-eight patients were transferred to the intensive care unit (ICU), and six patients died in our unit. CLD were not predictive of ICU hospitalization, but a significantly higher total mortality was observed (17.6% vs. 5.5%, P<0.05) in these patients. CONCLUSIONS: Our results suggest the lack of an over-representation of CLD in COVID-19, representing 40% of patients in this cohort and even within a pulmonology department. CLD were not a risk factor for ICU management. However, a tendency to higher global mortality was observed in COVID-19 patients with CLD. Further studies are warranted to determine the risk of COVID-19 for patients with comorbid CLD.

Cytokine mRNA expression during an in vitro response of human B lymphocytes: kinetics of B cell tumor necrosis factor alpha, interleukin (IL)6, IL-10, and transforming growth factor beta 1 mRNAs.

Expression of mRNA for eight cytokines was analyzed in an in vitro response-proliferation and Ig-secretion--of normal human B lymphocytes. This was made possible by the use of murine thymoma cells as helper cells in conjunction with human T cell supernatant, and the design of human DNA sequence-specific primers for RT-polymerase chain reaction. mRNAs for interleukin (IL)2 and IL-4, but also for IL-1 alpha and IL-1 beta remained undetectable during the whole culture period in highly purified B cells prepared by a three-step purification protocol. However, tumor necrosis factor alpha and IL-6 mRNAs peaked during days 1-3 after culture start and became undetectable after 5-6 d, shortly before bulk B cell proliferation started to decline. In contrast, transforming growth factor beta 1 mRNA, after a progressive increase during the first few days, and IL-10 mRNA, after a peak on days 1-3, remained detectable in immunoglobulin (Ig)-secreting cultures throughout the observation period of 22 d. Clonal analysis on 8-d cultures that had been seeded with single B cells by autocloning with the cell sorter, revealed that 85% of 77 B cell clones studied, expressed TGF-beta 1 mRNA, and only 19% IL-10 mRNA. These findings show a differentiation stage-related cytokine program during a B cell response, whereby (a) B cells can become activated without IL-1 alpha or IL-1 beta expression; (b) mRNA for positive (IL-10) and negative (TGF-beta 1) autoregulatory factors coexists in cell populations during the later phase of the response, although not necessarily in all B cell clones; and (c) normal Ig-secreting cells cease IL-6 expression in contrast to their malignant counterparts, myeloma cells.

BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth.

Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family, designated BAFF (for B cell activating factor belonging to the TNF family), which is expressed by T cells and dendritic cells. Human BAFF was mapped to chromosome 13q32-34. Membrane-bound BAFF was processed and secreted through the action of a protease whose specificity matches that of the furin family of proprotein convertases. The expression of BAFF receptor appeared to be restricted to B cells. Both membrane-bound and soluble BAFF induced proliferation of anti-immunoglobulin M-stimulated peripheral blood B lymphocytes. Moreover, increased amounts of immunoglobulins were found in supernatants of germinal center-like B cells costimulated with BAFF. These results suggest that BAFF plays an important role as costimulator of B cell proliferation and function.

Annoyance from industrial noise: indicators for a wide variety of industrial sources.

In the study of noises generated by industrial sources, one issue is the variety of industrial noise sources and consequently the complexity of noises generated. Therefore, characterizing the environmental impact of an industrial plant requires better understanding of the noise annoyance caused by industrial noise sources. To deal with the variety of industrial sources, the proposed approach is set up by type of spectral features and based on a perceptive typology of steady and permanent industrial noises comprising six categories. For each perceptive category, listening tests based on acoustical factors are performed on noise annoyance. Various indicators are necessary to predict noise annoyance due to various industrial noise sources. Depending on the spectral features of the industrial noise sources, noise annoyance indicators are thus assessed. In case of industrial noise sources without main spectral features such as broadband noise, noise annoyance is predicted by the A-weighted sound pressure level L(Aeq) or the loudness level L(N). For industrial noises with spectral components such as low-frequency noises with a main component at 100 Hz or noises with spectral components in middle frequencies, indicators are proposed here that allow good prediction of noise annoyance by taking into account spectral features.

Tropomyosin or not tropomyosin, what is the relevant allergen in house dust mite and snail cross allergies?

Since tropomyosin is cross reactive in many arthropods, it was assumed that this highly conserved protein could be responsible for cross reactions in house dust mite (HDM) allergic patients who experienced adverse reactions after crustacean and mollusc ingestion. Here we report two clinical cases where the role of tropomyosin is a matter of debate. In the first case, the clinical history, as well as the results of in vivo and in vitro investigations, are in favour of a shrimp allergy without any snail allergy in a patient sensitized to HDM. In the second, the clinical history and the cutaneous tests are in favour of an allergy to snails without any allergy to shrimps in a patient suffering from HDM allergies. The clinical presentation is different in shrimp and snail allergies. In shrimp allergy, symptoms are mainly urticaria or angio-oedema. In snail allergies, adverse reactions are especially severe asthma. Shrimp tropomyosin is a dominant allergen in crustaceans whereas has a much less prominent role in HDM sensitization. Cross reactivities between HDM and snails have been confirmed by inhibition experiments. However, tropomyosin appears to be a minor allergen or even is not involved in snail allergy. It is necessary to clarify the allergens shared between HDMI and snails. The effects of HDM immunotherapy in snail allergy are questioned. Knowledge of taxonomy can contribute to more precise evaluation of cross reactivities between crustaceans and molluscs.

Magnetic resonance imaging and spectroscopy of the rat hippocampus 1 month after exposure to 56Fe-particle radiation.

The response of the central nervous system to space radiation is largely unknown. The hippocampus, which is known for its critical role in learning and memory, was evaluated for its response to heavy-ion radiation. At 1 month, animals exposed to brain-only 56Fe-particle irradiation (0-4 Gy) were examined using contrast-enhanced T1 imaging (CET1), T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), and (1)H-magnetic resonance spectroscopy (MRS). Correlative histology was performed after imaging. The T2WI, DWI and CET1 images revealed no overt anatomical changes after irradiation. Quantitative analysis demonstrated a significant increase in T2 at 2 Gy compared to 0 Gy. The apparent diffusion coefficient (ADC) revealed an inverse dose-dependent quantitative change in water mobility. Compared to 0 Gy, the ADC increased 122% at 1 Gy and declined to 44% above control levels at 4 Gy. MRS showed a significant increase in the N-acetylaspartate/choline ratio at 4 Gy and a lactate peak. Histology demonstrated no overt pathological changes in neuronal and astrocyte populations. However, a significant inverse dose-dependent morphological change in the microglial population was detected in irradiated animals. Our results suggest that early tissue matrix modifications induced by 56Fe-particle radiation can be detected by MRI in the absence of evident histopathology. These changes may indicate fundamental changes in the structure and function of the hippocampus.

[Interest of admission blood sampling for the detection of somatic comorbidity in hospitalized psychiatric patients]. / Intérêt du bilan biologique d'entrée dans le dépistage de comorbidités chez les patients hospitalisés en psychiatrie.

INTRODUCTION: Elevated prevalence of somatic disorders among psychiatric patients is well known and studied since latest years. According to several studies, all-cause death risk is three to fivefold to that in the general population, and a somatic comorbidity was found in 30 to 60% of patients hospitalized in a psychiatric hospital, but was unknown in 50% of cases. OBJECTIVE: Our aim was to evaluate the interest of admission blood sampling analyses for the detection of somatic comorbidity, such as impaired glucose tolerance, diabetes mellitus, lipid abnormalities or infectious diseases among hospitalized psychiatric patients. DESIGN: During three months, laboratory tests (blood cell count, glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, sodium, potassium, chlorine, urea, creatinine, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, and TSH) were determined in admission blood samples from 366 patients of two psychiatric hospitals. Then, according to the blood results, other biological tests (iron, ferritin, etc.) were made. RESULTS: For 194 of the 366 blood samples included (53%), at least one biological abnormality was detected. Moreover, variations in haematological variables, glucose and lipid concentrations were the most frequent. We found that 45 (10.6%) of the patients had impaired glucose tolerance (glycaemia > or =1.10 g/l), 21 (5.7%) had glycaemia > or =1.26 g/l, and 76 (23%) had dyslipidemia (HDL-cholesterol < or =0.40 g/l, LDL-cholesterol > or =1.60 g/l, or triglycerides > or =1.50 g/l). None of them had used glucose or cholesterol lowering drugs before the blood sampling. Furthermore, low haemoglobin concentrations were detected in 34 patients (9.3%) and high white cell counts (above 12 g/l) in 26 patients (7.1%). CONCLUSION: Despite methodological limits, these results showed the frequency of somatic comorbidity in patients hospitalized in psychiatric hospitals. Thus, admission blood sampling would be likely to improve the detection of somatic disorders, such as diabetes mellitus, dyslipidemia, or infectious diseases.

[Is celecoxib a safe alternative for the Fernand Widal syndrome?] / Célécoxib, une alternative sûre pour les syndromes de Fernand Widal ?

The Fernand Widal syndrome is a set of associations between asthma, nasal polyposis and aspirin sensitivity. Selective cyclo-oxygenase 2 (COX 2) inhibitors are recognized as being a therapeutic alternative in cases needing analgesic or anti-inflammatory treatment. In a retrospective study, we have compiled data concerning oral provocation tests (OPT) undertaken with celecoxib, one of most the selective COX 2 inhibitors, in eight patients with the Fernand Widal syndrome. They were compared with twenty-seven control patients with sensitivity to aspirin or non-steroidal anti-inflammatories, manifesting as asthma, urticaria or rhino-conjunctivitis. Four patients with the Fernand Widal syndrome developed bronchospasm after taking the usually recommended daily dose of celecoxib while all the control patients tolerated it. The Fernand Widal patients who reacted during the OPT had a lower threshold of reactivity to aspirin, a more severe reaction with aspirin, and/or more severe asthma. In patients with the Fernand Widal syndrome, celecoxib is not always a possible alternative to non-steroidal anti-inflammatory drugs. Its introduction must be carried out in a hospital environment under medical supervision.

Astrochemical evolution along star formation: Overview of the IRAM Large Program ASAI.

Evidence is mounting that the small bodies of our Solar System, such as comets and asteroids, have at least partially inherited their chemical composition from the first phases of the Solar System formation. It then appears that the molecular complexity of these small bodies is most likely related to the earliest stages of star formation. It is therefore important to characterize and to understand how the chemical evolution changes with solar-type protostellar evolution. We present here the Large Program "Astrochemical Surveys At IRAM" (ASAI). Its goal is to carry out unbiased millimeter line surveys between 80 and 272 GHz of a sample of ten template sources, which fully cover the first stages of the formation process of solar-type stars, from prestellar cores to the late protostellar phase. In this article, we present an overview of the surveys and results obtained from the analysis of the 3 mm band observations. The number of detected main isotopic species barely varies with the evolutionary stage and is found to be very similar to that of massive star-forming regions. The molecular content in O- and C- bearing species allows us to define two chemical classes of envelopes, whose composition is dominated by either a) a rich content in O-rich complex organic molecules, associated with hot corino sources, or b) a rich content in hydrocarbons, typical of Warm Carbon Chain Chemistry sources. Overall, a high chemical richness is found to be present already in the initial phases of solar-type star formation.

Diagnosis of primary ciliary dyskinesia: When and how?

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare congenital disorder involving permanent ubiquitous structural and/or functional ciliary abnormalities. METHODS: A single-center retrospective study included 56 cases of PCD (respiratory form) out of a cohort of 280 patients with suspected PCD. The main features of history-taking and clinical examination were analyzed, to formulate a pragmatic diagnostic procedure, easy to implement in clinical practice. RESULTS: Chronic respiratory tract infectious symptoms are sensitive but non-specific for the diagnosis of PCD. Nasal brushing for phase-contrast microscopy study of ciliary morphology and activity proved to be a fast, easy, non-invasive, cost-effective and age-independent diagnostic method. In doubtful cases, depending on local availability, further tests are indicated: nasal nitric oxide level, electronic microscopy, genetic study and cell culture. CONCLUSIONS: In suspected PCD, there being no gold standard method of screening and early diagnosis, nasal brushing with ciliary study is contributive, alongside numerous other complementary tests, on condition that the clinician is experienced and results are interpreted in the light of clinical examination and history-taking.