Thorax 1991;46:459-461 459

heart disease.7 This report describes a boy Left bronchial who had had intractable wheezing from infancy as a result of widespread discrete areas

isomerism associated of bronchomalacia without bronchiectasis, Thorax: first published as 10.1136/thx.46.6.459 on 1 June 1991. Downloaded from and who also had some minor congenital with bronchomalacia, malformations and a rare combination of bronchial, atrial, and abdominal anatomical presenting with arrangements. We report this case because of the unusual anatomy and other congenital intractable wheeze malformations, and to emphasise the care needed in assessing wheezy children.

Philip Lee, Andrew Bush, John 0 Warner Case report This 12 year old boy was referred as a case of steroid resistant asthma. He had had recurrent episodes of coughing and noisy breathing from the age of 5 months, usually precipitated by an upper respiratory infection. At 22 months a Abstract murmur was noted during an episode of right The cause of the Williams Campbell syn- lower lobe pneumonia, and he subsequently drome (bronchomalacia with bronchi- underwent ligation ofa patent arterial duct. He ectasis) is controversial. A boy with subsequently developed wheezing in the early bronchomalacia, bifid ribs, and left bron- morning, a chronic cough, and breathlessness chial isomerism presented with intract- on minimal exertion, despite inhaling sal- able wheeze mimicking asthma. The butamol and beclomethasone. A trial of oral combination of the abdominal, bron- prednisolone, 30 mg daily for one week, failed chial, and atrial anatomy seen in this to improve his symptoms. The only physical child has been described only once finding of note was widespread inspiratory and previously. The coexistence of these expiratory wheeze, more pronounced on the congenital abnormalities in this boy left. Investigations included a normal full supports a congenital cause for the blood count, an erythrocyte sedimentation rate Williams Campbell syndrome. The need of 5 mm in one hour, and normal immuno- to assess wheezy children critically is globulins; no serological evidence of viral

emphasised. infection, and normal results from an auto- http://thorax.bmj.com/ antibody screen. The chest radiograph showed In 1960 Williams and Campbell described five bifid left first and fourth ribs, but was otherwise children with widespread bronchomalacia and unremarkable. A barium swallow and a com- bronchiectasis,' postulating that the primary puted tomogram of the thorax were normal. defect was a developmental deficiency of Lung function test results, expressed as % bronchial wall cartilage."2 Others believe that predicted,8 were: forced expiratory volume in bronchiectasis secondary to pertussis, one second (FEVI) 33%; forced vital capacity measles, or adenovirus infection is the main (FVC) 65% ratio total (FEVI/FVC 43%); lung on October 1, 2021 by guest. Protected copyright. abnormality, causing secondary broncho- capacity (TLC) 72%, residual volume 91%, malacia.3 All previous children with the and carbon monoxide transfer 89%. Specific Williams Campbell syndrome have had airways conductance (sGaw) was 1 15 s-I kPa-' normal bronchial anatomy-that is, the (normal > 1-3 s- kPa-1). Ten second accessible morphologically right and left lung in the lung volume was 87% of TLC, and carbon right and the left hemithorax respectively. monoxide transfer/litre of accessible volume The anatomical arrangement of the lungs may (Kco) was 135% predicted. The flow-volume be of three other forms, however: situs inver- loop showed (fig 1) substantially reduced sus, right isomerism (two morphologically expiratory flow, particularly at low lung right lungs), and left isomerism (two volumes, with relatively well preserved in- morphologically left lungs). The morphology spiratory flows. Fibreoptic bronchoscopy with of the bronchial tree is variously defined on the bronchography showed a normal trachea with basis of the length of the main bronchus left isomerism (fig 2). Localised areas in both before the takeoff of the upper lobe bronchus, main bronchi narrowed to slits on expiration, the relation between the pulmonary artery and reopening on inspiration so that the broncho- the upper lobe Department of bronchus, and the number of scope could easily be passed through to the Paediatrics, National lobes in the lung." These anatomical more normal bronchial tree beyond. Broncho- Heart and Lung arrangements are of clinical importance graphy showed a single discrete proximal area Institute and Royal right isomerism may be associated with Brompton and of narrowing in the left sided bronchial tree, National Heart and asplenia (Ivemark's syndrome) and left and multiple additional areas of variable nar- Lung Hospital, London isomerism with polysplenia.4 Both left and rowing in the subsegmental bronchi beyond SW3 6HP right isomerism may be associated with P Lee the narrowing in the right sided main bron- A Bush malrotation of abdominal viscera and congen- chus. There was no evidence of bronchiectasis. J 0 Warner ital heart disease.45 Atrial situs and bronchial An echocardiogram was normal, showing the Reprint requests to: situs are normally identical,6 an important usual arrangement of atria. Abdominal Dr Bush consideration in the sequential description of ultrasound showed normal visceral positions Accepted 15 February 1991 cardiac anatomy in the setting of congenital with a single spleen. 460 Lee, Bush, Warner

in retrospect were attributable to broncho- malacia. The lung function tests showed relatively well preserved inspiratory flows and sGaw despite severe expiratory obstruction. Thorax: first published as 10.1136/thx.46.6.459 on 1 June 1991. Downloaded from The close agreement between accessible lung volume and TLC suggests that there was no substantial small airways disease, and the Kco was not reduced, suggesting that the lung parenchyma was probably not severely dis- eased. Bilateral bronchography and computed tomography of the thorax showed no evidence of bronchiectasis, but did show large airway disease-namely, discrete areas ofnarrowing of both main bronchi and numerous localised subsegmental areas of bronchomalacia on the right side, similar to those in the original description of the syndrome.' The areas of malacia were very localised and separated by regions ofnormal bronchi, suggesting that they were merely secondary to raised intrapleural Figure 1 Theflow-volume loop. The predicted loop is given by the dotted line, and is based on the work of Denison et al." There is disproportionate reduction in expiratory pressure from another cause. The boy also had flow rates, with a normal residual volume (RV) and slightly reduced total lung capacity other congenital anomalies (left bronchial (TLC). INSP-inspiration; EXP-expiration. isomerism, bifid ribs, and a patent arterial duct), all of which strongly support a con- genital origin. Also of interest is the discrepancy between the abdominal and thoracic anatomy in this Discussion boy. All previous patients with the Williams There has been disagreement in published Campbell syndrome have had a normal atrial reports about whether the Williams Campbell and bronchial arrangement. Our patient had syndrome is truly congenital or acquired secon- normal abdominal viscera with a single nor- dary to a viral infection.23 In favour of a mally placed spleen, normal atria, but left congenital cause is its occurrence in two bronchial isomerism. These anatomical siblings9 and the report of a four month old features have been described only once before.6

baby with symptoms from birth and general- We were in doubt about how to manage this http://thorax.bmj.com/ ised bronchomalacia without bronchiectasis.'0 child. There are no published reports of bron- The negative serological results in this child chial stenting in children, other than in the and other patients'2 suggest that a viral cause is setting ofheart-lung transplantation. It was felt unlikely, but infection cannot be excluded as an that consideration of this procedure should if aetiological factor in some cases. Our patient possible be postponed until adulthood. He is had had symptoms from 5 months ofage, which therefore having regular chest physiotherapy on October 1, 2021 by guest. Protected copyright.

Figure 2 Appearance of the bronchoscopic bronchogram: (a) right sided lung; (b) left sided lung. There is left bronchial isomerism and narrowed regions in both main bronchi, with more widespread narrowing of the segmental bronchi of the right sided lung. Contrast remains in the normally placed stomach from a previous barium swallow. Left bronchial isomerism associated with bronchomalacia presenting with intractable wheeze 461

treatment of infection in an ectasis due to extensive deficiency of bronchial cartilage. with aggressive any Arch Dis Child 1972;47:423-8. attempt to prevent progression to bronchi- 3 Capitanio MA. Commentary. J Pediatr 1975;87:233-4. ectasis. 4 Landing BH, Lawrence TK, Payne CV, Wells TR. Bron- chial anatomy in syndromes with abnormal visceral situs, In summary, this child had bronchomalacia abnormal spleen and congenital heart disease. Am J Thorax: first published as 10.1136/thx.46.6.459 on 1 June 1991. Downloaded from of the pattern seen in the Williams Campbell Cardiol 1971;28:456-62. and other 5 Deanfield JE, Leanage R, Stroobant J, Chrispin AR, Taylor syndrome congenital abnormalities, JFN, Macartney FJ. Use ofhigh kilovoltage filtered beam previously not encountered together, which radiographs for detection ofbronchial situs in infants and supports a congenital cause for this syndrome. young children. Br Heart J 1980;44:577-83. 6 Caruso G, Becker AE. How to determine atrial situs? The case also emphasises the need critically to Considerations initiated by 3 cases of absent spleen with assess all wheezy children. For many years this discordant anatomy between bronchi and atria. Br Heart J boy was to have and was even 1979;41:559-67. thought asthma, 7 Shinebourne EA, Macartney FJ, Anderson RH. Sequential treated with systemic corticosteroids. Flow- chamber localisation: the logical approach to diagnosis in volume loops can show large airway disease congenital heart disease. Br Heart J 1976;38:327-40. 8 Cotes JE. Lung function: assessment and application in and, as in this child, may alert the clinician to medicine. 4th ed. Oxford: Blackwell, 1979. the possibility of another diagnosis. 9 Wayne KS, Taussig LM. Probable familial congenital bronchiectasis due to cartilage deficiency (Williams Campbell syndrome). Am Rev Respir Dis 1976;114:15-22. 10 Agosti E, de Filippi G, Fior R, Chiussi F. Generalised I Williams H, Campbell P. Generalised bronchiectasis familial bronchomalacia. Acta Paediatr Scand 1974; associated with deficiency ofcartilage in the bronchial tree. 63:616-8. Arch Dis Child 1960;35:182-91. 11 Denison DM, Du Bois R, Sawicka E. Pictures in the mind. 2 Williams HI, Landau LI, Phelan PD. Generalised bronchi- Br J Dis Chest 1983;77:35-50.

Thorax 1991;46:461-2 205 x 109/l; some neutrophils were Malignant pleural hypogranular and some platelets were noted to be large on the blood film. Bone marrow effusion in chronic examination showed hypercellularity, active erythropoiesis, active myelopoiesis with 28% myelomonocytic monocytes or monocytoid cells and an increased number of megakaryocytes with leukaemia abnormal forms, including micronuclear and

mononuclear forms. Cytogenetic studies http://thorax.bmj.com/ showed an abnormal chromosome constitu- tion: 46,XX,del(7)(q22), del(20)(ql 1). Clot- A Manoharan ting studies gave normal results, arterial blood gas analysis showed hypoxaemia (oxygen ten- sion 5-7 kPa), and results of liver function Abstract tests were abnormal. Pleural fluid biochemical A case of malignant pleural effusion due investigations showed: protein 38 g/l, glucose to chronic myelomonocytic leukaemia is 3.7 mmol/l, and lactic dehydrogenase 482 reported. (normal 55-120) U/30 1. Cytological examina- on October 1, 2021 by guest. Protected copyright. tion of pleural fluid (figure) showed features of chronic myelomonocytic leukaemia. A pleural Malignant pleural effusions are extremely rare biopsy was not done. Excision biopsy of an in patients with chronic myelomonocytic axillary lymph node showed diffuse mono- leukaemia, a haemopoietic stem cell disorder cytoid leukaemic infiltration, with frequent with myeloproliferative and myelodysplastic mitotic figures. features.' 2 During the four days when investigations were in progress, repeated left sided thoracocenteses were required for symp- Case report tomatic relief, and her white blood cell count A 52 year old woman presented with a three increased from 87 to 130 x 109/1. She was week history of lethargy, weakness, and started on treatment with low doses of progressive dyspnoea. Examination disclosed cytarabine (10 mg/M2 every 12 hours sub- bilateral pleural effusions, greater on the left cutaneously), 6-thioguanine (40 mg every 12 than the right side, minimal generalised lym- hours orally), and etoposide (100 mg a day phadenopathy, and splenomegaly of 7 cm. orally) for 10 days, with good results. Six Chest radiography and computed tomography weeks later she was clinically well with Department of showed mediastinal lymphadenopathy and reduced splenomegaly (4 cm); her chest Clinical Haematology, bilateral pleural effusions. Abdominal com- radiograph showed a small opacity at the left St George Hospital, puted tomography showed hepatospleno- Kogarah, Sydney, base posteriorly. Her haemoglobin (1 1-5 g/dl), New South Wales 2217, megaly and para-aortic lymphadenopathy. white blood count (32 x 109/1), and platelets Australia A full blood count showed: haemoglobin 12-8 (60 x 109/1) had also improved. Further treat- A Manoharan g/dl, white blood cells 87 x 109/l (neutrophils ment, at the patient's request, consisted only Reprint requests to: 52%, monocytes 27%, blasts 4%, promyelo- of intermittent low dose single agent therapy Dr Manoharan cytes 1%, myelocytes 4%, metamyelocytes with 6-thioguanine or hydroxyurea. Accepted 11 January 1991 4%, and band forms 8%), and platelets In March 1989 four months after her initial